28092-52-6

Usage

InChI:InChI=1/C19H18N2O2S/c22-18-17-16(13-24-18)20(11-14-7-3-1-4-8-14)19(23)21(17)12-15-9-5-2-6-10-15/h1-10,16-17H,11-13H2/t16-,17-/m0/s1

Synthetic route

(3aS,6aR)-1,3-dibenzyltetrahydro-1H-furo[3,4-d]imidazole-2,4-dione (28092-62-8) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
With ammonium xanthate at 120℃; for 9h; Reagent/catalyst; Temperature; Inert atmosphere;	98%
With sodium thioacetate In N,N-dimethyl-formamide at 130℃; for 6h; Temperature; Solvent; Reagent/catalyst; Inert atmosphere;	96.5%
With tiolacetic acid; potassium hydroxide In N,N-dimethyl-formamide; benzene at -10 - 70℃; for 2h; Inert atmosphere;	94%

(4R,5R)-1,3-dibenzyl-5-(mercaptomethyl)imidazolidin-2-one-4-carboxylic acid (112878-95-2) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
With pyridine; dicyclohexyl-carbodiimide; trifluoroacetic acid In chloroform for 5h; Heating;	93%
With pyridine; dicyclohexyl-carbodiimide; trifluoroacetic acid In chloroform at 10℃; for 1h;	80%
With pyridine; toluene-4-sulfonic acid; dicyclohexyl-carbodiimide In toluene at 25 - 62℃; for 20h;	75%

(2S)-2-[(4R)-3-benzyl-2-oxathiazolidin-4-yl]-2-benzylaminoacetamide hydrochloride → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
In N,N-dimethyl-formamide at 120℃; for 5h;	91%
In DMF (N,N-dimethyl-formamide) at 100℃; for 3h;	n/a

cis-1,3-Dibenzyltetrahydro-2H-thieno[3,4-d]imidazole-2,4,6-trione (324012-37-5) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
With (R)-BINAL-H In tetrahydrofuran at -78℃; for 6h; Reduction;	83%

(4R,5R)-1,3-dibenzyl-3,3a,6,6a-tetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (541508-62-7) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
With pyridine In chloroform at 25℃; for 23h;	75%
With pyridine In chloroform at 60℃; for 6h;	88.1 g
In pyridine; chloroform at 20℃; for 23h;

C21H23IN2O3 → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
With HNaS*(x)H2O In N,N-dimethyl-formamide at 20℃; for 17h; Inert atmosphere;	60%

(+)-<3aS-(3α,4α,6aα)>-1,3-dibenzyl-3a,4,6,6a-tetrahydro-4-hydroxy-1H-thieno<3,4-d>imidazol-2(3H)-one (132203-12-4) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
With dimethyl sulfoxide; triethylamine; trifluoroacetic anhydride 1.) dichloromethane, -78 deg C, 1 h, then -60 deg C, 1 h, 2.) -78 deg C, 5 min, then warming to room temperature over 1.5 h; Yield given. Multistep reaction;
With acetic anhydride; dimethyl sulfoxide at 50℃; for 1.5h; Yield given;
With dimethyl sulfoxide; triethylamine; trifluoroacetic anhydride Multistep reaction;

2-[(4R)-3-benzyl-2-oxathiazolidin-4-yl]-2-benzylaminoacetonitrile (777940-99-5) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 93 percent / aq. H2O2; K2CO3 / dimethylsulfoxide; CH2Cl2 / 6 h / 20 °C 2: dimethylformamide / 1 h / 90 °C 3: 95.1 g / aq. HCl / dimethylformamide / 3 h / 90 °C 4: 80 percent / pyridine; TFA; DCC / CHCl3 / 1 h / 10 °C View Scheme
Multi-step reaction with 5 steps 1: 93 percent / aq. H2O2; K2CO3 / dimethylsulfoxide; CH2Cl2 / 6 h / 20 °C 2: dimethylformamide / 1 h / 90 °C 3: 95.1 g / aq. HCl / dimethylformamide / 3 h / 90 °C 4: 42 percent / pyridine; TFA; DCC / CHCl3 / 1 h / 25 °C 5: 75 percent / pyridine / CHCl3 / 23 h / 25 °C View Scheme

(2R)-2-[(4R)-3-benzyl-2-oxathiazolidin-4-yl]-2-benzylaminoacetamide (541508-59-2) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: dimethylformamide / 1 h / 90 °C 2: 95.1 g / aq. HCl / dimethylformamide / 3 h / 90 °C 3: 80 percent / pyridine; TFA; DCC / CHCl3 / 1 h / 10 °C View Scheme
Multi-step reaction with 4 steps 1: dimethylformamide / 1 h / 90 °C 2: 95.1 g / aq. HCl / dimethylformamide / 3 h / 90 °C 3: 42 percent / pyridine; TFA; DCC / CHCl3 / 1 h / 25 °C 4: 75 percent / pyridine / CHCl3 / 23 h / 25 °C View Scheme
Multi-step reaction with 2 steps 1.1: dimethylformamide / 1 h / 90 °C 1.2: 95 percent / HCl 2.1: 93 percent / DCC; pyridine; TFA / CHCl3 / 5 h / Heating View Scheme
Multi-step reaction with 4 steps 1: dimethylformamide / 1 h / 90 °C 2: 95.1 g / conc. HCl / dimethylformamide / 3 h / 90 °C 3: DCC; pyridine; TFA / CHCl3 / 1 h / 10 °C 4: 88.1 g / pyridine / CHCl3 / 6 h / 60 °C View Scheme

(4R,5R)-1,3-dibenzyl-2-oxo-5-(mercaptomethyl)imidazolidin-4-carboxamide (541508-64-9) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95.1 g / aq. HCl / dimethylformamide / 3 h / 90 °C 2: 80 percent / pyridine; TFA; DCC / CHCl3 / 1 h / 10 °C View Scheme
Multi-step reaction with 3 steps 1: 95.1 g / aq. HCl / dimethylformamide / 3 h / 90 °C 2: 42 percent / pyridine; TFA; DCC / CHCl3 / 1 h / 25 °C 3: 75 percent / pyridine / CHCl3 / 23 h / 25 °C View Scheme
Multi-step reaction with 2 steps 1: 0.44 g / aq. HCl / acetic acid / 2 h / 110 °C 2: 75 percent / p-TsOH*H2O; DCC; pyridine / toluene / 20 h / 25 - 62 °C View Scheme
Multi-step reaction with 3 steps 1: 95.1 g / conc. HCl / dimethylformamide / 3 h / 90 °C 2: DCC; pyridine; TFA / CHCl3 / 1 h / 10 °C 3: 88.1 g / pyridine / CHCl3 / 6 h / 60 °C View Scheme

(4S,5R)-1,3-dibenzyl-1H-furo[3,4-d]imidazole-2,4,6-trione (26339-42-4) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 90 percent / toluene / 5 h / Heating 2.1: 82 percent / BF3*Et2O; NaH; chiral polymer-supported oxazaborolidine / tetrahydrofuran / 3 h / Heating 3.1: NaBH4 / ethanol / 4 h / 50 °C 3.2: 90 percent / aq. H2SO4 / ethanol / 1 h / 80 °C 4.1: 82 percent / potassium n-butylthioxanthogenate / N,N-dimethyl-acetamide / 6 h / 125 °C View Scheme
Multi-step reaction with 4 steps 1: 3-(3,5-bis-trifluoromethyl-phenylamino)-4-{[(S)-(6-methoxy-quinolin-4-yl)-((R)-5-vinyl-1-aza-bicyclo[2.2.2]oct-2-yl)-methyl]-amino}-cyclobut-3-ene-1,2-dione / tert-butyl methyl ether / 24 h / 25 °C / Inert atmosphere 2: calcium chloride / ethanol / 0 - 25 °C / Inert atmosphere 3: hydrogenchloride / water / 0.5 h / 55 °C / Inert atmosphere 4: thiobenzoic acid potassium salt / N,N-dimethyl-formamide / 2 h / 150 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: C27H36N4OS / tert-butyl methyl ether / 10 h / 25 °C / Inert atmosphere 2: potassium borohydride; lithium bromide / tetrahydrofuran / 7 h / 40 °C / Inert atmosphere 3: N,N-dimethyl acetamide / 6 h / 125 °C / Inert atmosphere View Scheme

benzylamine (100-46-9) + polymer-supported formate → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 90 percent / toluene / 5 h / Heating 2.1: 82 percent / BF3*Et2O; NaH; chiral polymer-supported oxazaborolidine / tetrahydrofuran / 3 h / Heating 3.1: NaBH4 / ethanol / 4 h / 50 °C 3.2: 90 percent / aq. H2SO4 / ethanol / 1 h / 80 °C 4.1: 82 percent / potassium n-butylthioxanthogenate / N,N-dimethyl-acetamide / 6 h / 125 °C View Scheme

(3aS,6R,6aR)-1,3,5-tribenzyl-6-hydroxytetrahydro-4H-pyrrolo[3,4-d]imidazole-2,4(1H)-dione (634188-84-4) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: NaBH4 / ethanol / 4 h / 50 °C 1.2: 90 percent / aq. H2SO4 / ethanol / 1 h / 80 °C 2.1: 82 percent / potassium n-butylthioxanthogenate / N,N-dimethyl-acetamide / 6 h / 125 °C View Scheme
Multi-step reaction with 2 steps 1.1: KBH4; CaCl2 / ethanol / 4 h / 20 °C 1.2: 85 percent / HCl / ethanol; H2O / 0.75 h / 55 - 60 °C 2.1: 88 percent / CH3SC(S)SK / 6 h / 120 °C View Scheme
Multi-step reaction with 2 steps 1.1: KBH4; LiCl / tetrahydrofuran / 2 h / 20 °C 1.2: 90 percent / aq. HCl / tetrahydrofuran / 0.5 h / 55 °C 2.1: 93 percent / potassium ethylthioxanthogenate / dimethylformamide / 3 h / 125 °C View Scheme

1,3,5-tribenzyl-2,4,6-trioxopyrrolo<3,4-d>imidazoline (26511-17-1) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 82 percent / BF3*Et2O; NaH; chiral polymer-supported oxazaborolidine / tetrahydrofuran / 3 h / Heating 2.1: NaBH4 / ethanol / 4 h / 50 °C 2.2: 90 percent / aq. H2SO4 / ethanol / 1 h / 80 °C 3.1: 82 percent / potassium n-butylthioxanthogenate / N,N-dimethyl-acetamide / 6 h / 125 °C View Scheme
Multi-step reaction with 3 steps 1.1: 85 percent / LiH; (1S,2S)-1-(4-NO2C6H4)-2-NH2-3-(triphenylmethoxy)propan-1-ol; BF3*Et2O / tetrahydrofuran / Heating 2.1: KBH4; CaCl2 / ethanol / 4 h / 20 °C 2.2: 85 percent / HCl / ethanol; H2O / 0.75 h / 55 - 60 °C 3.1: 88 percent / CH3SC(S)SK / 6 h / 120 °C View Scheme
Multi-step reaction with 3 steps 1.1: 91 percent / polymer-supported-C6H4-4-SO2-[(S)-2-CPh2OH-pyrrolidin-1-yl]; BH3*SMe2 / tetrahydrofuran / 6 h / Heating 2.1: KBH4; LiCl / tetrahydrofuran / 2 h / 20 °C 2.2: 90 percent / aq. HCl / tetrahydrofuran / 0.5 h / 55 °C 3.1: 93 percent / potassium ethylthioxanthogenate / dimethylformamide / 3 h / 125 °C View Scheme

cis-1,3-dibenzyl-2-oxoimidazolidine-4,5-dicarboxylic acid (51591-75-4, 634188-82-2) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 98 percent / Ac2O / xylene / 13 h / Heating 2.1: 90 percent / toluene / 5 h / Heating 3.1: 82 percent / BF3*Et2O; NaH; chiral polymer-supported oxazaborolidine / tetrahydrofuran / 3 h / Heating 4.1: NaBH4 / ethanol / 4 h / 50 °C 4.2: 90 percent / aq. H2SO4 / ethanol / 1 h / 80 °C 5.1: 82 percent / potassium n-butylthioxanthogenate / N,N-dimethyl-acetamide / 6 h / 125 °C View Scheme
Multi-step reaction with 4 steps 1.1: 95 percent / conc. H2SO4 / benzene / 6 h / Heating 2.1: 80 percent / immobilized PLE on Eupergit C(R); aq. NaOH / aq. phosphate buffer; methanol / 45 h / 30 °C / pH 8 3.1: LiEt3BH / tetrahydrofuran / 0 - 20 °C 3.2: 88 percent / aq. HCl / tetrahydrofuran / 1 h / 45 °C 4.1: 80 percent / EtOC(S)SK / N,N-dimethyl-acetamide / 7 h / 125 °C View Scheme
Multi-step reaction with 4 steps 1.1: 90 percent / pyridine / xylene / 8 h / Heating 2.1: 85 percent / LiH; (1S,2S)-1-(4-NO2C6H4)-2-NH2-3-(triphenylmethoxy)propan-1-ol; BF3*Et2O / tetrahydrofuran / Heating 3.1: KBH4; CaCl2 / ethanol / 4 h / 20 °C 3.2: 85 percent / HCl / ethanol; H2O / 0.75 h / 55 - 60 °C 4.1: 88 percent / CH3SC(S)SK / 6 h / 120 °C View Scheme

(4S,5R)-1,3-bisbenzyl-2-oxo-5-(methoxycarbonyl)imidazolidin-4-carboxylic acid (83889-77-4) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: LiEt3BH / tetrahydrofuran / 0 - 20 °C 1.2: 88 percent / aq. HCl / tetrahydrofuran / 1 h / 45 °C 2.1: 80 percent / EtOC(S)SK / N,N-dimethyl-acetamide / 7 h / 125 °C View Scheme
Multi-step reaction with 3 steps 1: calcium chloride / ethanol / 0 - 25 °C / Inert atmosphere 2: hydrogenchloride / water / 0.5 h / 55 °C / Inert atmosphere 3: thiobenzoic acid potassium salt / N,N-dimethyl-formamide / 2 h / 150 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: potassium borohydride; lithium bromide / tetrahydrofuran / 7 h / 40 °C / Inert atmosphere 2: N,N-dimethyl acetamide / 6 h / 125 °C / Inert atmosphere View Scheme

dimethyl cis-1,3-dibenzyl-2-oxoimidazolidine-4,5-dicarboxylate (56198-73-3) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 80 percent / immobilized PLE on Eupergit C(R); aq. NaOH / aq. phosphate buffer; methanol / 45 h / 30 °C / pH 8 2.1: LiEt3BH / tetrahydrofuran / 0 - 20 °C 2.2: 88 percent / aq. HCl / tetrahydrofuran / 1 h / 45 °C 3.1: 80 percent / EtOC(S)SK / N,N-dimethyl-acetamide / 7 h / 125 °C View Scheme

(R)-3-benzyl-2-oxothiazolidine-4-carbaldehyde (541508-56-9) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 99 percent / NaHSO3 / ethyl acetate; H2O / 18 h / 20 °C 2.1: dimethylformamide / 1 h / 90 °C 2.2: 95 percent / HCl 3.1: 93 percent / DCC; pyridine; TFA / CHCl3 / 5 h / Heating View Scheme
Multi-step reaction with 3 steps 1: 99 percent / NaHSO3 / ethyl acetate; H2O / 18 h / 20 °C 2: 91 percent / dimethylformamide / 5 h / 120 °C View Scheme
Multi-step reaction with 6 steps 1: 96 percent / toluene 2: 93 percent / H2O2; K2CO3 / dimethylsulfoxide 3: dimethylformamide / 1 h / 90 °C 4: 95.1 g / conc. HCl / dimethylformamide / 3 h / 90 °C 5: DCC; pyridine; TFA / CHCl3 / 1 h / 10 °C 6: 88.1 g / pyridine / CHCl3 / 6 h / 60 °C View Scheme

(R)-3-benzyl-4-hydroxymethyl-2-oxothiazolidine (541508-55-8) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 90 percent / DCC; pyridine; TFA / dimethylsulfoxide; ethyl acetate / 3 h / 50 °C 2.1: 99 percent / NaHSO3 / ethyl acetate; H2O / 18 h / 20 °C 3.1: dimethylformamide / 1 h / 90 °C 3.2: 95 percent / HCl 4.1: 93 percent / DCC; pyridine; TFA / CHCl3 / 5 h / Heating View Scheme
Multi-step reaction with 4 steps 1: 90 percent / DCC; pyridine; TFA / dimethylsulfoxide; ethyl acetate / 3 h / 50 °C 2: 99 percent / NaHSO3 / ethyl acetate; H2O / 18 h / 20 °C 3: 91 percent / dimethylformamide / 5 h / 120 °C View Scheme
Multi-step reaction with 7 steps 1: 89 percent / DCC; pyridine; TFA / dimethylsulfoxide / 25 - 45 °C 2: 96 percent / toluene 3: 93 percent / H2O2; K2CO3 / dimethylsulfoxide 4: dimethylformamide / 1 h / 90 °C 5: 95.1 g / conc. HCl / dimethylformamide / 3 h / 90 °C 6: DCC; pyridine; TFA / CHCl3 / 1 h / 10 °C 7: 88.1 g / pyridine / CHCl3 / 6 h / 60 °C View Scheme

Sodium; (R)-((S)-3-benzyl-2-oxo-thiazolidin-4-yl)-hydroxy-methanesulfonate → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: dimethylformamide / 1 h / 90 °C 1.2: 95 percent / HCl 2.1: 93 percent / DCC; pyridine; TFA / CHCl3 / 5 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 91 percent / dimethylformamide / 5 h / 120 °C View Scheme

benzylamine (100-46-9) + N-acetyl-N'-(3,4-dichlorophenylhaloacetyl)-hydrazide → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 90 percent / pyridine / xylene / 8 h / Heating 2.1: 85 percent / LiH; (1S,2S)-1-(4-NO2C6H4)-2-NH2-3-(triphenylmethoxy)propan-1-ol; BF3*Et2O / tetrahydrofuran / Heating 3.1: KBH4; CaCl2 / ethanol / 4 h / 20 °C 3.2: 85 percent / HCl / ethanol; H2O / 0.75 h / 55 - 60 °C 4.1: 88 percent / CH3SC(S)SK / 6 h / 120 °C View Scheme
Multi-step reaction with 4 steps 1.1: 95 percent / 4 Angstroem molecular sieves / xylene / 12 h / Heating 2.1: 91 percent / polymer-supported-C6H4-4-SO2-[(S)-2-CPh2OH-pyrrolidin-1-yl]; BH3*SMe2 / tetrahydrofuran / 6 h / Heating 3.1: KBH4; LiCl / tetrahydrofuran / 2 h / 20 °C 3.2: 90 percent / aq. HCl / tetrahydrofuran / 0.5 h / 55 °C 4.1: 93 percent / potassium ethylthioxanthogenate / dimethylformamide / 3 h / 125 °C View Scheme

(1R,2S,4R)-3-benzyl-4-carbamoyl-2-oxo-2-phenylimidazo[1,5-c]thiazolidine (646512-43-8) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: Zn; AcOH / 2 h / 100 °C 2: 0.44 g / aq. HCl / acetic acid / 2 h / 110 °C 3: 75 percent / p-TsOH*H2O; DCC; pyridine / toluene / 20 h / 25 - 62 °C View Scheme

benzylamino-2-[(2R,4R)-3-phenoxycarbonyl-2-phenylthiazolidin-4-yl]acetonitrile → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 5 steps 1: 60 percent / K2CO3; aq. H2O2 / dimethylsulfoxide / 17 h / 25 °C 2: 60 percent / dimethylformamide / 2 h / 100 °C 3: Zn; AcOH / 2 h / 100 °C 4: 0.44 g / aq. HCl / acetic acid / 2 h / 110 °C 5: 75 percent / p-TsOH*H2O; DCC; pyridine / toluene / 20 h / 25 - 62 °C View Scheme

(R)-2-benzylamino-2-[(2R,4R)-3-phenoxycarbonyl-2-phenylthiazolidin-4-yl]acetamide (646512-51-8) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 60 percent / dimethylformamide / 2 h / 100 °C 2: Zn; AcOH / 2 h / 100 °C 3: 0.44 g / aq. HCl / acetic acid / 2 h / 110 °C 4: 75 percent / p-TsOH*H2O; DCC; pyridine / toluene / 20 h / 25 - 62 °C View Scheme

(R)-3-benzyl-2-oxothiazolidine-4-carboxylic acid (98155-23-8) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 8 steps 1: 89 percent / Me2S*BH3 2: 89 percent / DCC; pyridine; TFA / dimethylsulfoxide / 25 - 45 °C 3: 96 percent / toluene 4: 93 percent / H2O2; K2CO3 / dimethylsulfoxide 5: dimethylformamide / 1 h / 90 °C 6: 95.1 g / conc. HCl / dimethylformamide / 3 h / 90 °C 7: DCC; pyridine; TFA / CHCl3 / 1 h / 10 °C 8: 88.1 g / pyridine / CHCl3 / 6 h / 60 °C View Scheme

(2R)-2-[(4R)-3-benzyl-2-oxathiazolidin-4-yl]-2-benzylaminoacetonitrile (541508-57-0) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 5 steps 1: 93 percent / H2O2; K2CO3 / dimethylsulfoxide 2: dimethylformamide / 1 h / 90 °C 3: 95.1 g / conc. HCl / dimethylformamide / 3 h / 90 °C 4: DCC; pyridine; TFA / CHCl3 / 1 h / 10 °C 5: 88.1 g / pyridine / CHCl3 / 6 h / 60 °C View Scheme

benzyl bromide (100-39-0) + polymer-bound NMe3(1+)*SCN(1-) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 84 percent / NaH / dimethylformamide / 17 h / 20 °C 2: 92 percent / AcSK / dimethylformamide View Scheme

(3aS,6aR)-tetrahydro-1H-furo[3,4-d]imidazole-2,4-dione (159912-63-7) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 84 percent / NaH / dimethylformamide / 17 h / 20 °C 2: 92 percent / AcSK / dimethylformamide View Scheme

(4R,5S)-1-benzyloxycarbonylamino-4-benzyloxymethoxy-methylimidazolidin-2-one-5-carboxylic acid (429691-52-1) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 80 percent / H2 / 10 percent Pd(OH)2/C / aq. methanol / 17 h / 20 °C / 2574.28 Torr 2: 84 percent / NaH / dimethylformamide / 17 h / 20 °C 3: 92 percent / AcSK / dimethylformamide View Scheme

ethyl 5-bromovalerate (14660-52-7) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → ethyl (3aS,4Z,6aR)-5-(1,3-dibenzyl-2,3,3a,4,6,6a-hexahydro-2-oxo-1H-thieno[3,4-d]imidazole-5-ylidene)pentanoate (292151-18-9)

Conditions	Yield
Stage #1: ethyl 5-bromovalerate With chloro-trimethyl-silane; tetra-(n-butyl)ammonium iodide; sodium iodide; zinc In tetrahydrofuran; ethylene dibromide at 25 - 65℃; for 8.3h; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione With palladium 10% on activated carbon In tetrahydrofuran; ethylene dibromide; N,N-dimethyl-formamide; toluene at 25℃; for 15h;	100%

(3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) + potassium thioacetate (10387-40-3) → biotin (58-85-5)

Conditions	Yield
In water at 0 - 60℃; Temperature;	97%

ethyl 5-iodopentanoate (41302-32-3) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → ethyl (3aS,4Z,6aR)-5-(1,3-dibenzyl-2,3,3a,4,6,6a-hexahydro-2-oxo-1H-thieno[3,4-d]imidazole-5-ylidene)pentanoate (292151-18-9)

Conditions	Yield
Stage #1: ethyl 5-iodopentanoate With chloro-trimethyl-silane; bromine; zinc In tetrahydrofuran; toluene at 50 - 60℃; for 1h; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione With N,N-dimethyl-formamide; palladium on activated charcoal In tetrahydrofuran; toluene at 25 - 30℃; for 18h; Fukuyama coupling reaction; Further stages.;	95%
Stage #1: ethyl 5-iodopentanoate With bromine; zinc In tetrahydrofuran; toluene at 50 - 60℃; for 1h; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione; palladium on activated charcoal In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 28 - 40℃; for 5h; Stage #3: With hydrogenchloride In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 20℃; for 1h;	94%
Stage #1: ethyl 5-iodopentanoate With chloro-trimethyl-silane; ethylene dibromide; zinc In tetrahydrofuran at 30 - 60℃; for 1h; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione; palladium hydroxide - carbon In N,N-dimethyl-formamide; toluene at 25 - 35℃; for 2h; Fukuyama coupling reaction; Stage #3: With toluene-4-sulfonic acid In toluene at 20℃; for 1.5h;	87%
Stage #1: ethyl 5-iodopentanoate With chloro-trimethyl-silane; zinc In tetrahydrofuran; toluene at 50℃; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione; palladium on activated charcoal In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 30℃; Fukuyama coupling; Stage #3: With hydrogenchloride In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 20℃; Further stages.;	95 % Chromat.

1-bromo-4-ethoxybutane (3448-29-1) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → C25H30N2O2S

Conditions	Yield
Stage #1: 1-bromo-4-ethoxybutane With iodine; magnesium In tetrahydrofuran for 1h; Inert atmosphere; Reflux; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione In tetrahydrofuran for 2h; Reflux; Inert atmosphere; Stage #3: With sulfuric acid In tetrahydrofuran; water for 3h; Reflux;	95%

(3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) + 5-ethoxy-5-oxopentylzinc iodide → 5-[(3aR,6aS)-1,3-Dibenzyl-2-oxo-hexahydro-thieno[3,4-d]imidazol-(6E)-ylidene]-pentanoic acid ethyl ester (333355-49-0)

Conditions	Yield
Stage #1: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione; 5-ethoxy-5-oxopentylzinc iodide; palladium dihydroxide In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 30℃; Fukuyama coupling reaction; Stage #2: With hydrogenchloride In tetrahydrofuran; N,N-dimethyl-formamide; toluene	92%

(5-ethoxy-5-oxopentyl)zinc(II) iodide (109976-46-7) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → 5-[(3aR,6aS)-1,3-Dibenzyl-2-oxo-hexahydro-thieno[3,4-d]imidazol-(6E)-ylidene]-pentanoic acid ethyl ester (333355-49-0)

Conditions	Yield
Stage #1: (5-ethoxy-5-oxopentyl)zinc(II) iodide; (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione With N,N-dimethyl-formamide In tetrahydrofuran; toluene at 25 - 35℃; for 2h; Fukuyama Coupling; Stage #2: With hydrogenchloride In toluene	92%

ethyl 5-bromovalerate (14660-52-7) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → ethyl 5-{(3aS,6aR)-1,3-dibenzyl-4-hydroxy-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl}-pentanoate (1041862-06-9)

Conditions	Yield
Stage #1: ethyl 5-bromovalerate With iodine; zinc In tetrahydrofuran; toluene at 40 - 50℃; for 3.5 - 4.5h; Fukuyama coupling reaction; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione; anion exchange resin D296 dispersed nano-palladium In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 30 - 35℃; for 12h; Stage #3: With water In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 20℃; for 0.5h; Product distribution / selectivity;	87%
Stage #1: ethyl 5-bromovalerate With iodine; zinc In tetrahydrofuran; toluene at 50℃; for 4.5 - 5.5h; Fukuyama coupling reaction; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione; anion exchange resin D290 dispersed nano-palladium In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 30 - 40℃; for 24h; Stage #3: With water In tetrahydrofuran; N,N-dimethyl-formamide; toluene Product distribution / selectivity;	85.7%

Vinyl bromide (593-60-2) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → (3aR,8aS)-tetrahydro-1,3-bis(phenylmethyl)-1H-thiepino-[3,4-d]imidazole-2,8(3H,4H)-dione (1187740-53-9)

Conditions	Yield
Stage #1: Vinyl bromide With magnesium In tetrahydrofuran at 20℃; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione In tetrahydrofuran at 0 - 20℃;	86%

1,4-dibromo-butane (110-52-1) + carbon dioxide (124-38-9) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → 5-((3aS,4S,6aR)-1,3-dibenzyl-4-hydroxy-2-oxo-1H-thieno[3,4-d]imidazole-4-yl)pentanoic acid

Conditions	Yield
Stage #1: 1,4-dibromo-butane With iodine; magnesium In tetrahydrofuran for 3.5h; Grignard Reaction; Inert atmosphere; Reflux; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione In tetrahydrofuran at -30 - -20℃; for 1h; Inert atmosphere; Stage #3: carbon dioxide With acetic acid at -30 - 50℃; for 3.5h; Inert atmosphere;	86%

5-bromopentanoic acid (2067-33-6) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → ethyl 5-{(3aS,6aR)-1,3-dibenzyl-4-hydroxy-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl}-pentanoate (1041862-06-9)

Conditions	Yield
Stage #1: 5-bromopentanoic acid With iodine; zinc In tetrahydrofuran; toluene at 50℃; for 2.5h; Fukuyama cross-coupling reaction; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione In tetrahydrofuran; tyoluene; N,N-dimethyl-formamide at 35℃; for 10h; Fukuyama cross-coupling reaction;	85%

ethyl 5-iodopentanoate (41302-32-3) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → biotin (58-85-5)

Conditions	Yield
Stage #1: ethyl 5-iodopentanoate With bromine; zinc In tetrahydrofuran; toluene at 40℃; for 1h; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione With palladium 10% on activated carbon In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 28 - 40℃; for 5h; Further stages;	85%

C5H10ClMgO(1-)*Cl(1-)*Mg(2+) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → C24H30N2O3S

Conditions	Yield
In tetrahydrofuran at 20℃; for 5h; Temperature; Inert atmosphere; Cooling with ice;	83%

(5-ethoxy-5-oxopentyl)zinc(II) iodide (109976-46-7) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → ethyl (3aS,4Z,6aR)-5-(1,3-dibenzyl-2,3,3a,4,6,6a-hexahydro-2-oxo-1H-thieno[3,4-d]imidazole-5-ylidene)pentanoate (292151-18-9)

Conditions	Yield
With bis(acetylacetonate)nickel(II) In monoethylene glycol diethyl ether; toluene at 20℃; for 15h; Product distribution; Further Variations:; Reagents; Solvents; Temperatures;	81%

(4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → (3aS,4Z,6aR)-5-{hexahydro-1,3-dibenzyl-2-oxo-4H-thieno[3,4-d]imidazol-4-ylidene}pentanoic acid (452100-87-7)

Conditions	Yield
Stage #1: (4-carboxybutyl)triphenylphosphonium bromide With potassium tert-butylate In toluene at 25℃; for 0.75h; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione In toluene at 135℃; for 7h; Wittig reaction;	81%

5-iodovaleronitrile (6727-75-9) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazol-2(3H)-one-4-ylidenepentane nitrile (634188-85-5)

Conditions	Yield
Stage #1: 5-iodovaleronitrile With chloro-trimethyl-silane; ethylene dibromide; zinc In tetrahydrofuran at 30℃; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione; nickel on carbon In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 20℃; for 30h; Fukuyama coupling reaction;	80%

2-(4-bromobutyl)-4,5-dihydrooxazole + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → 5-[(3aS,6aR)-1,3-dibenzyl-2-oxo-tetrahydro-1H-thieno[3,4-d]imidazol-4-ylidene]pentanoic acid

Conditions	Yield
With magnesium In tetrahydrofuran; ethylene dibromide Inert atmosphere; Reflux;	78.2%

C5H10BrMgO(1-)*Cl(1-)*Mg(2+) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → C24H30N2O3S

Conditions	Yield
In tetrahydrofuran at 20℃; for 5h; Inert atmosphere; Cooling with ice;	77%

diethylzinc (557-20-0) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → (3aS,4Z,6aR)-2-[1,3-dibenzyl-2,3,3a,4,6,6a-hexahydro-2-oxo-1H-thieno[3,4-d]imidazol-4-ylidene]-ethane (1041865-17-1)

Conditions	Yield
With bromine; N,N-dimethyl-formamide; zinc; palladium diacetate In tetrahydrofuran; toluene at 45℃; for 2h; Fukuyama coupling reaction;	76%

(3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) + benzyl 5-iodopentanoate (118058-70-1) → benzyl (3aS,6aR)-5-(1,3-dibenzyl-2,3,3a,4,6,6a-hexahydro-2-oxo-4-hydroxyl-1H-thieno[3,4-d]imidazol-4-yl)pentanoate (1042432-14-3)

Conditions	Yield
Stage #1: benzyl 5-iodopentanoate With bromine; zinc In tetrahydrofuran; toluene at 50 - 60℃; for 1h; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione; nanopalladium catalyst In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 30℃; for 24h; Fukuyama coupling; Further stages.;	75%
Stage #1: benzyl 5-iodopentanoate With bromine; zinc In tetrahydrofuran; toluene at 10 - 60℃; for 1h; Fukuyama coupling reaction; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione; anion exchange resin D290 dispersed nano-palladium In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 30℃; for 24h; Stage #3: With water; ammonium chloride In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 20℃; for 0.5h; Product distribution / selectivity;	75%
Stage #1: benzyl 5-iodopentanoate With iodine; zinc In N,N-dimethyl-formamide at 80℃; for 3h; Fukuyama coupling reaction; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione; anion exchange resin D296 dispersed nano-palladium In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 30℃; for 24h; Stage #3: With water; ammonium chloride In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 20℃; for 0.5h; Product distribution / selectivity;	75%

ethyl 5-bromovalerate (14660-52-7) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → ethyl (3aS,4RS,6aR)-5-(1,3-dibenzyl-2,3,3a,4,6,6a-hexahydro-4-hydroxy-2-oxo-1H-thieno[3,4-d]imidazol-4-yl)pentanoate (1236230-80-0)

Conditions

Yield

Stage #1: ethyl 5-bromovalerate With iodine; zinc In N,N-dimethyl-formamide at 80℃; for 4.5h; Fukuyama coupling; Inert atmosphere; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione With palladium 10% on activated carbon In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 30℃; for 30h; Fukuyama coupling; Inert atmosphere; Stage #3: With water; ammonium chloride In tetrahydrofuran; N,N-dimethyl-formamide; toluene

75%

5-iodovaleronitrile (6727-75-9) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → C24H25N3OS

Conditions	Yield
Stage #1: 5-iodovaleronitrile With chloro-trimethyl-silane; zinc; ethylene dibromide In tetrahydrofuran at 20 - 30℃; for 0.75h; Fukuyama coupling reaction; Heating / reflux; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 35h;	73%

Iodomethyl methyl ether (13057-19-7) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → (3aS,4S,6aR)-1,3-dibenzyl-2-oxohexahydro-1H-thieno[3,4-d]imidazole-4-carbaldehyde (154097-01-5)

Conditions	Yield
Stage #1: Iodomethyl methyl ether With magnesium In dibutyl ether; toluene at 45℃; for 1h; Grignard reaction; Stage #2: (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione In dichloromethane; dibutyl ether at 15℃; for 3h; Stage #3: With hydrogenchloride In dibutyl ether; toluene for 3h; Heating;	70%

C5H10IMgO(1-)*Cl(1-)*Mg(2+) + (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione (28092-52-6) → C24H30N2O3S

Conditions	Yield
In tetrahydrofuran at 20℃; for 5h; Inert atmosphere; Cooling with ice;	65%

Upstream product

• 129301-68-4 (+/-)-1,3-dibenzyl-5c-formyl-2-oxo-imidazolidine-4r-carboxylic acid 
• 28092-55-9 6ξ-acetoxy-1,3-dibenzyl-(3ar,6ac)-tetrahydro-furo[3,4-d]imidazole-2,4-dione 
• 51591-75-4 cis-1,3-dibenzyl-2-oxoimidazolidine-4,5-dicarboxylic acid 
• 28092-62-8 (3aS,6aR)-1,3-dibenzyltetrahydro-1H-furo[3,4-d]imidazole-2,4-dione 
• 132203-08-8 4-<(S)-1-Phenylethoxy>-<3aS-(3aα,4α,6aα)>-tetrahydro-1,3-bis(phenylmethyl)-1H-thieno<3,4-d>imidazol-2(3H)-one 
• 21035-72-3 (+)-cis-1,3-dibenzyl-hexahydro-1H-thieno[3,4-d]imidazole-2,4-dione 
• 21035-77-8 (+/-)-(3aα,4α,6aα)-1,3-dibenzyl-3a,4,6,6a-tetrahydro-4-hydroxy-1H-thieno<3,4-d>imidazol-2(3H)-one 
• 100-44-7 benzyl chloride 
• 157378-76-2 C₁₉H₂₀N₂O₄ 
• 132150-93-7 4-<(3β,5α)-Cholestan-3-yloxy>-<3aS-(3aα,4α,6aα)>-tetrahydro-1,3-bis(phenylmethyl)-1H-thieno<3,4-d>imidazol-2(3H)-one 
• 132203-10-2 Methyl (S)-α-<<3aS-(3aα,4α,6aα)>-2-hexahydro-2-oxo-1,3-bis(phenylmethyl)-1H-thieno<3,4-d>imidazol-4-yloxy>benzeneacetate 
• 132203-11-3 (S)-α-<<3aS-(3aα,4α,6aα)>-2-Hexahydro-2-oxo-1,3-bis(phenylmethyl)-1H-thieno<3,4-d>imidazol-4-yloxy>benzeneacetic acid 
• 103621-13-2 (+/-)-(3aα,4α,6aα)-4-Chlorotetrahydro-1,3-bis(phenylmethyl)-1H-thieno<3,4-d>imidazol-2(3H)-one 
• 429691-52-1 (4R,5S)-1-benzyloxycarbonylamino-4-benzyloxymethoxy-methylimidazolidin-2-one-5-carboxylic acid 

Downstream Products

• 1041862-06-9 ethyl 5-{(3aS,6aR)-1,3-dibenzyl-4-hydroxy-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl}-pentanoate 
• 292151-18-9 ethyl (3aS,4Z,6aR)-5-[1,3-dibenzyl-2,3,3a,4,6,6a-hexahydro-2-oxo-1H-thieno[3,4-d]imidazol-5-ylidene]-pentanoate 
• 634188-85-5 (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazol-2(3H)-one-4-ylidenepentane nitrile 
• 863203-60-5 5-((3aS,6aR)-1,3-dibenzyl-4-hydroxy-2-oxohexyl-1H-furo[3,4-d]imidazol-4-yl)pentenoic acid 
• 1041865-17-1 (3aS,4Z,6aR)-2-[1,3-dibenzyl-2,3,3a,4,6,6a-hexahydro-2-oxo-1H-thieno[3,4-d]imidazol-4-ylidene]-ethane 
• 1236230-80-0 ethyl (3aS,4RS,6aR)-5-(1,3-dibenzyl-2,3,3a,4,6,6a-hexahydro-4-hydroxy-2-oxo-1H-thieno[3,4-d]imidazol-4-yl)pentanoate 
• 58-85-5 biotin 
• 33719-11-8 (3aR)-1,3-dibenzyl-2-oxo-(3ar,8ac,8bc)-decahydro-thieno[1',2':1,2]thieno[3,4-d]imidazolium; bromide 
• 1042432-14-3 benzyl (3aS,6aR)-5-(1,3-dibenzyl-2,3,3a,4,6,6a-hexahydro-2-oxo-4-hydroxyl-1H-thieno[3,4-d]imidazol-4-yl)pentanoate 
• 115495-39-1 (3aS,6aR)-1,3-dibenzyl-4-pentylidene-1H-hexahydrothieno<3,4-d>imidazole-2-one 
• 115587-50-3 (3aS,4S,6aR)-1,3-dibenzyl-4-n-pentyl-1H-tetrahydrothieno<3,4-d>imidazole-2(3H)-one 
• 31099-31-7 (3aS,4S,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2(3H)-one-4-ylpentane nitrile 
• 153991-84-5 (E)-5-[(3aR,6aS)-1,3-Dibenzyl-2-oxo-hexahydro-thieno[3,4-d]imidazol-(6E)-ylidene]-pent-3-enoic acid 
• 367276-82-2 (3aS,4R,6aR)-1,3-dibenzyl-4-[(1E,3E)-4-methoxycarbonyl-1,3-butanedienyl]-1H-tetrahydrothieno[3,4-d]imidazol-2(3H)-one 

Relevant academic research and scientific papers

METHOD FOR PRODUCING THIOLACTONE COMPOUND

PROBLEM TO BE SOLVED: To provide a method for producing a thiolactone compound at high yield. SOLUTION: A method for producing a thiolactone compound includes bringing a lactone compound, in which S in a compound of the formula (II) is replaced with O, into contact with acetic acid alkali metal salt in a first organic solvent to make a first mixture; and bringing the first mixture into contact with a thiocarboxylic acid to make a second mixture including the thiolactone compound of the formula (II) [R1 and R2 each denote H, a benzyl group, or a substituted benzyl group]. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT

Practical Synthesis of (+)-Biotin Key Intermediate by Calcium Borohydride Reduction and Temperature-Dependent Purity Upgrade during Crystallization

An expedient synthesis of a key intermediate for (+)-biotin has been accomplished through high-yielding reduction of chiral imide with calcium borohydride and efficient isolation of the desired isomer by crystallization at a specific temperature where only undesired isomer was converted to soluble anhydrate while the desired isomer kept unchanged as a less soluble monohydrate.

METHOD FOR PRODUCING THIOLACTONE COMPOUND

To provide a production method for obtaining a high-purity thiolactone compound at good yields.SOLUTION: A method for producing a thiolactone compound includes crystallizing and extracting a thiolactone compound of the following formula in an alcohol solvent with a boiling point of 85°C or higher, where R1 and R2 each denote H or a ureine protection group such as a benzyl group.SELECTED DRAWING: None

Preparation method of sodium thioacetate and method for preparing thiolactone by using sodium thioacetate

The invention relates to the field of organic chemistry, and discloses a preparation method of sodium thioacetate and a method for preparing thiolactone from sodium thioacetate, which are characterized in that the method comprises the following steps: in the presence of a first solvent, reacting RONa with thioacetic acid; wherein R is an alkyl group of C1 to C4, preferably an alkyl group of C1 toC2. The method has the advantages of simple process, cheap and easily available raw materials and high product yield, and provides convenience for industrial production of sodium thioacetate. The thiolactone prepared from the sodium thioacetate prepared by the method has the advantages of high reaction yield, few side reactions and high product purity.

ESTER DERIVATIVE, AND METHOD FOR PRODUCING THIOLACTONE DERIVATIVE

PROBLEM TO BE SOLVED: To provide an ester derivative, that is a novel intermediate for producing thiolactone derivative from a lactone derivative, and a method for producing thiolactone derivative. SOLUTION: The ester derivative (2) is obtained via halogenation and esterification of a lactone derivative (1). (In the formula, R1 and R2 represent benzyl. R3 is alkyl and X is halogen.). SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT

Amide derivatives, the amide derivative and (by machine translation)

[Problem] amide derivative useful as an intermediate for synthesis of biotin, and method for producing an amide derivative. [Solution] the corresponding alcohol derivative, mesyl agent, such as agent manufactured by reacting sulfonyl, an amide derivative represented by the formula. (In the formula R1 And R2 The, same or different, substituted or unsubstituted benzyl group, R3 Is, substituted or unsubstituted phenyl group, X is, thiol groups, [meshirokishi[meshirokishi] group, a trifluoromethanesulfonyloxy group, p - [toshirokishi[toshirokishi] groups, such as halogen groups are selected from the group. )[Drawing] no (by machine translation)

Synthesis method of thiolactone

The invention discloses a synthesis method of thiolactone. The method includes the following step of conducting the reaction shown in the description on a compound II and a thio agent under the protection of inert gas to obtain a compound I. In the synthesis method, complete reaction can be carried out without adding any organic solvent as the reaction solvent, operation and after-treatment are simple, the product purity is high, the yield is high, the environmental pollution is small, and the method has broad industrial application prospects.

Process development and scale-up for the preparation of roche thiolactone: Key intermediate for (+)-biotin

The main objective of this paper was to report a short and efficient synthesis of Roche thiolactone starting from cis-1,3-dibenzyltetrahydro-2H-furo-[3,4-d]-imidazole-2,4,6-trione (2) with an overall yield of 74%. The optimized synthetic route consists of three chemical steps and the final process of thiolactonization of (3aS,6aR)-lactone 4 using xanthate ionic liquid in solvent-free conditions to furnish Roche thiolactone 1 not only features the yield improvement of 1 by optimizing reaction variables but also highlights simplifying the subsequent workup procedure.

Method for Producing Intermediate of Biotin and Method for Producing Biotin

In the method, a trione compound represented by the following formula (1) is (i) reduced by NaAlH2(OCH2CH2OCH3)2 and subsequently further reduced by a metal borohydride salt, or (ii) reduced by calcium borohydride, thereby producing an amide alcohol compound represented by the following formula (3) (wherein, R1 and R2 may be the same or different and each represents a hydrogen atom or a protecting group of an ureylene group; R4 represents an alkyl group, an aralkyl group, or an aryl group; and each of R5, R6, and R7 represents a hydrogen atom, an alkyl group, an alkoxy group, or a halogen atom).

A biotin intermediate THIONES method for the preparation of

The invention relates to a preparation method for the biotin intermediate thioketone. The preparation method comprises the following steps: with a mixed solution of potassium thioacetate and thioacetic acid as a thiolizing reagent and mixing the thiolizing reagent with (3aS,6aS)1,3-dibenzyl-tetrahydro-4H-furo[3,4-d]imidazole-2,4(1H)-dione; recovering benzene from a mixed system and carrying out dehydration; and finally carrying out a sulfuration reaction under the protection of nitrogen so as to obtain (3aS,6aS)1,3-dibenzyl-tetrahydro-4H-thieno[3,4-d]imidazole-2,4(1H)-dione. According to the invention, the mixed solution of potassium thioacetate and thioacetic acid is used as the thiolizing reagent, (3aS,6aS)1,3-dibenzyl-tetrahydro-4H-furo[3,4-d]imidazole-2,4(1H)-dione is added, benzene low temperature reflux and a water separator are employed for water separation and removal of water in the system, so a high purity product is obtained. The method provided by the invention overcomes the disadvantages of easy deterioration and decomposition of the thiolizing reagent, great influence of water in the system on the sulfuration reaction, etc. and has the advantages of improved sulfuration efficiency, good product quality and high yield.