154212-61-0

Basic information

• Product Name: (S)-2-(3-((2-Isopropylthiazol-4-yl)methyl)-3-methylureido)-3-methylbutanoic acid
• Synonyms: N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)Methyl)aMino)carbonyl)-L-valine (MTV-III);MTV-III N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)Methyl)aMino)carbonyl)-L-valine;(MTV-III) N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)Methyl)aMino)carbonyl)-L-valin;MTV;L-Valine,N-[[methyl[[2-(1-methylethyl)-4-thiazolyl]methyl]amino]carbonyl]-;N-[2-Isopropylthiazol-4-ylmethyl(methyl)carbamoyl]-L-valine;(s)-2-(3-((2-isopropylthiazol-4-yl)methyl)-3-methylureido)-3-methylbutanoic acid;(S)-2-(3-((2-ISOPROPYLTHIAZOL-4-YL)METHYL)-3-METHYLUREIDO)-3-METHYLBUTANOIC ACID,98%
• CAS NO: 154212-61-0
• Molecular Formula: C₁₄H₂₃N₃O₃S
• Molecular Weight: 313.42
• EINECS: 1806241-263-5
• Product Categories: Amino Acids & Derivatives;Heterocycles;Intermediates
• Mol File: 154212-61-0.mol
• Article Data: 11

Chemical Properties

• Boiling Point: 532.573 °C at 760 mmHg
• Flash Point: 275.89 °C
• Appearance: /
• Density: 1.193
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.545
• Storage Temp.: 2-8°C
• PKA: 4.39±0.10(Predicted)
• CAS DataBase Reference: (S)-2-(3-((2-Isopropylthiazol-4-yl)methyl)-3-methylureido)-3-methylbutanoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-2-(3-((2-Isopropylthiazol-4-yl)methyl)-3-methylureido)-3-methylbutanoic acid(154212-61-0)
• EPA Substance Registry System: (S)-2-(3-((2-Isopropylthiazol-4-yl)methyl)-3-methylureido)-3-methylbutanoic acid(154212-61-0)

Safety Data

• Hazardous Substances Data: 154212-61-0(Hazardous Substances Data)

Usage

Chemical Properties

Light Yellow Oil

Uses

Different sources of media describe the Uses of 154212-61-0 differently. You can refer to the following data:
1. N-[[N-Methyl-N-[(2-isopropyl]-4-thiazolyl)methyl)amino]carbonyl-L-valine Carboxylic Acid (Ritonavir EP Impurity A) is an intermediate in the synthesis of Ritonavir.
2. An intermediate in the synthesis of Ritonavir.

InChI:InChI=1/C14H23N3O3S/c1-8(2)11(13(18)19)16-14(20)17(5)6-10-7-21-12(15-10)9(3)4/h7-9,11H,6H2,1-5H3,(H,16,20)(H,18,19)/t11-/m0/s1

Synthetic route

N-((N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine methyl ester (154248-99-4) → N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0)

Conditions	Yield
Stage #1: N-((N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine methyl ester With lithium hydroxide In tetrahydrofuran; water at 20℃; for 1.5h; Stage #2: With hydrogenchloride; water In tetrahydrofuran	93%
With lithium hydroxide In 1,4-dioxane for 0.5h; Ambient temperature;
With lithium hydroxide; water In 1,4-dioxane at 25℃; for 1h;

(2S)-3-Methyl-2-(phenoxycarbonyl)aminobutyric acid (126147-70-4) + N-methyl-N-<(2-isopropyl-4-thiazolyl)methyl>amine (154212-60-9) → N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0)

Conditions	Yield
With NaH In tetrahydrofuran; water; toluene	83%
With NaH In tetrahydrofuran; methanol; isopropyl alcohol	24%
With NaH In tetrahydrofuran
In tetrahydrofuran; water; acetonitrile

LiOH monohydrate + (2S)-3-Methyl-2-(phenoxycarbonyl)aminobutyric acid (126147-70-4) + N-methyl-N-<(2-isopropyl-4-thiazolyl)methyl>amine (154212-60-9) + phenol (108-95-2) → N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran; water; toluene	82%

(S)-3-methyl-2-[(2,2,2-trichloroethoxy)carbonylamino]butyric acid (78221-33-7) + N-methyl-N-<(2-isopropyl-4-thiazolyl)methyl>amine (154212-60-9) → N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0)

Conditions	Yield
With triethylamine In tetrahydrofuran at 50 - 60℃; for 6h; Green chemistry;	81%

(2S)-3-Methyl-2-(phenoxycarbonyl)aminobutyric acid (126147-70-4) + N-methyl-N-<(2-isopropyl-4-thiazolyl)methyl>amine (154212-60-9) + phenol (108-95-2) → N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran; n-heptane; water; toluene	78%

L-valine methylester hydrochloride (6306-52-1) + Sasrin Fmoc-valine → N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 4-methylmorpholine / CH2Cl2 / Ambient temperature 2: DMAP, Et3N / tetrahydrofuran / 2 h / Heating 3: 0.50 M aq. LiOH / dioxane / 0.5 h / Ambient temperature View Scheme

N-methyl-N-<(2-isopropyl-4-thiazolyl)methyl>amine (154212-60-9) → N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: DMAP, Et3N / tetrahydrofuran / 2 h / Heating 2: 0.50 M aq. LiOH / dioxane / 0.5 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine; 1,1'-carbonyldiimidazole 2: sodium hydroxide; methanol View Scheme
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine; 1,1'-carbonyldiimidazole 2: sodium hydroxide / methanol View Scheme

N-<<(4-nitrophenyl)oxy>carbonyl>-L-valine methyl ester (162537-10-2) → N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: DMAP, Et3N / tetrahydrofuran / 2 h / Heating 2: 0.50 M aq. LiOH / dioxane / 0.5 h / Ambient temperature View Scheme

4-(Chloromethyl)-2-isopropylthiazole Hydrochloride → N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: H2O / 1 h 2: DMAP, Et3N / tetrahydrofuran / 2 h / Heating 3: 0.50 M aq. LiOH / dioxane / 0.5 h / Ambient temperature View Scheme

tert-butyl methyl ether (1634-04-4) + (2S)-3-Methyl-2-(phenoxycarbonyl)aminobutyric acid (126147-70-4) + N-methyl-N-<(2-isopropyl-4-thiazolyl)methyl>amine (154212-60-9) → N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0)

Conditions	Yield
With hydrogenchloride; NaH In tetrahydrofuran; water; toluene

LiOH monohydrate + (2S)-3-Methyl-2-(phenoxycarbonyl)aminobutyric acid (126147-70-4) + N-methyl-N-<(2-isopropyl-4-thiazolyl)methyl>amine (154212-60-9) → N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0)

Conditions	Yield
In tetrahydrofuran; n-heptane; water; toluene	16.6 kg (83.8%)

aqueous LiOH + N-((N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine methyl ester (154248-99-4) → N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane; dichloromethane	1.1 g (81%)

L-valine methylester hydrochloride (6306-52-1) → N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine; 1,1'-carbonyldiimidazole 2: sodium hydroxide; methanol View Scheme

N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → N-[N-methyl-N-[(2-isopropyl-4-thiazolyl)methyl]aminocarbonyl]-L-valine chloride

Conditions	Yield
With thionyl chloride In dichloromethane; N,N-dimethyl-formamide at 0 - 10℃; for 1h;	98.1%
With thionyl chloride; triethylamine In ethyl acetate at 45℃; for 3h; Solvent; Temperature; Reagent/catalyst;

N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) + (2S,3S,5S)-5-Amino-2-(N-((5-thiazolyl)-methoxycarbonyl)amino)-3-hydroxy-1,6-diphenylhexane (144164-11-4) → ritonavir (155213-67-5)

Conditions	Yield
Stage #1: N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine With N-ethyl-N,N-diisopropylamine; diisopropyl-carbodiimide at 27℃; for 0.5h; Stage #2: (2S,3S,5S)-5-Amino-2-(N-((5-thiazolyl)-methoxycarbonyl)amino)-3-hydroxy-1,6-diphenylhexane for 7h; Temperature;	91.5%
With diethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In butanone at 41℃; for 0.666667h; Concentration; Temperature;	87.4%
With N-ethyl-N'-(3-diethylaminopropyl)-carbodiimide; 1-hydroxybenzotriazol-hydrate In tetrahydrofuran for 16h; Ambient temperature; Yield given;
Stage #1: N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine With pivaloyl chloride; triethylamine In dichloromethane at 0 - 10℃; Inert atmosphere; Large scale; Stage #2: With dmap In dichloromethane at 0 - 10℃; for 0.5h; Large scale; Stage #3: (2S,3S,5S)-5-Amino-2-(N-((5-thiazolyl)-methoxycarbonyl)amino)-3-hydroxy-1,6-diphenylhexane In dichloromethane at 25 - 35℃; Large scale;

C19H27N3O2S (1004316-72-6) + N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → C33H48N6O4S2

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran	87%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine

((1S,2S,4S)-4-amino-1-benzyl-2-hydroxy-5-phenyl-pentyl)-carbamic acid tert-butyl ester (144163-88-2) + N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → C37H53N5O5S

Conditions	Yield
Stage #1: N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine With triethylamine; p-toluenesulfonyl chloride In dichloromethane at 0 - 10℃; for 3h; Green chemistry; Stage #2: ((1S,2S,4S)-4-amino-1-benzyl-2-hydroxy-5-phenyl-pentyl)-carbamic acid tert-butyl ester With triethylamine In dichloromethane at 0 - 20℃; for 6h; Green chemistry;	86%

C24H29N3O2S (1004318-14-2) + N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → C38H50N6O4S2

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;	71%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine

N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-4-(E-hydroxyiminomethyl)-N-(isobutyl)benzenesulfonamide (890904-63-9) + N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → (2S)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}amino)-3-methylbutanamide

Conditions	Yield
With 4-methyl-morpholine In DMF (N,N-dimethyl-formamide); dichloromethane at 25℃; for 16h;	53%

N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → C23H34N6O4S2

Conditions

Yield

Stage #1: ((5-thiazolyl)methyl)-(4-nitrophenyl)carbonate; 1-t-Butoxycarbonylpiperazine With N-ethyl-N,N-diisopropylamine In acetonitrile at 25℃; for 12h; Stage #2: With hydrogenchloride; water In 1,4-dioxane; ethyl acetate at 25℃; for 12h; Stage #3: N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 25℃; for 12h;

45%

C7H11N3O2S*ClH (1004317-04-7) + N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → C21H32N6O4S2

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 25℃; for 12h;	38%

(piperidin-4-yl)carbamic acid tert-butyl ester (73874-95-0) + N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → C24H36N6O4S2

Conditions

Yield

Stage #1: (piperidin-4-yl)carbamic acid tert-butyl ester; ((5-thiazolyl)methyl)-(4-nitrophenyl)carbonate With N-ethyl-N,N-diisopropylamine In acetonitrile at 25℃; for 12h; Stage #2: With hydrogenchloride; water In 1,4-dioxane; ethyl acetate at 25℃; for 12h; Stage #3: N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 25℃; for 12h;

36%

N-Boc-1,3-diaminopropane (75178-96-0) + N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → C22H34N6O4S2

Conditions

Yield

Stage #1: N-Boc-1,3-diaminopropane; ((5-thiazolyl)methyl)-(4-nitrophenyl)carbonate With N-ethyl-N,N-diisopropylamine In acetonitrile at 25℃; for 12h; Stage #2: With hydrogenchloride; water In 1,4-dioxane; ethyl acetate at 25℃; for 12h; Stage #3: N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 25℃; for 12h;

34%

N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) + (2S,3S,5S)-5-(t-butyloxycarbonylamino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-3-hydroxy-1,6-diphenylhexane (162849-95-8) → (2S,3S,5S)-3-[O-[N-[N-methyl-N-[(2-isopropyl-4-thiazolyl)methyl]amino]carbonyl]-L-valyloxy]-5-[N-[(tert-butyloxy)carbonyl]amino]-2-[N-[(5-thiazolyl)methoxycarbonyl]amino]-1,6-diphenyl-3-hydroxyhexane (566939-06-8)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In chloroform at 20℃;	27%

C19H27N3O2S (1004316-71-5) + N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → C33H48N6O4S2

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran	20%

C13H23N3O2S (1004317-31-0) + N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → C27H44N6O4S2

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;	2%

N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) + (S)-4-((2R,3S)-3-Amino-2-hydroxy-4-phenyl-butyl)-3-tert-butylcarbamoyl-piperazine-1-carboxylic acid tert-butyl ester (159572-17-5) → (S)-3-tert-Butylcarbamoyl-4-((2R,3S)-2-hydroxy-3-{(S)-2-[3-(2-isopropyl-thiazol-4-ylmethyl)-3-methyl-ureido]-3-methyl-butyrylamino}-4-phenyl-butyl)-piperazine-1-carboxylic acid tert-butyl ester (251112-23-9)

Conditions	Yield
With TEA; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide

C11H19N3O2S (1004317-30-9) + N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → C25H40N6O4S2

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;

(2R,5R)-1,6-diphenylhexane-2,5-diamine (144186-34-5) + N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → C32H45N5O2S (1004318-11-9) + C46H66N8O4S2 (1004318-10-8)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 12h;

C23H25N3O2S + N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → C37H46N6O4S2

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine

C9H15N3O2S (1004318-31-3) + N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → C23H36N6O4S2

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine

C23H27N3O2S (1004318-32-4) + N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → C37H48N6O4S2

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine

1-benzylamino-3-{benzyl[(1,3-thiazol-5-ylmethoxy)carbonyl]amino}propane (1004318-33-5) + N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → C36H46N6O4S2

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;

N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) → N'-[(1S)-1-[[[(1S,2R)-3-[(2S)-2-[[(1,1-Dimethylethyl)amino]carbonyl]-1-piperazinyl]-2-hydroxy-1-(phenylmethyl)propyl]amino]carbonyl]-2-methylpropyl]-N-methyl-N-[2-(1-methylethyl)-4-thiazolylmethyl]urea (251112-24-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: EDC, TEA 2: TFA View Scheme

Upstream product

• 78221-33-7 (S)-3-methyl-2-[(2,2,2-trichloroethoxy)carbonylamino]butyric acid 
• 154212-60-9 N-methyl-N-<(2-isopropyl-4-thiazolyl)methyl>amine 
• 126147-70-4 (2S)-3-Methyl-2-(phenoxycarbonyl)aminobutyric acid 
• 108-95-2 phenol 
• 1634-04-4 tert-butyl methyl ether 
• 65386-28-9 4-(Chloromethyl)-2-isopropylthiazole Hydrochloride 
• 162537-10-2 N-<<(4-nitrophenyl)oxy>carbonyl>-L-valine methyl ester 
• 6306-52-1 L-valine methylester hydrochloride 
• 154248-99-4 N-((N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine methyl ester 

Downstream Products

• 1551453-85-0 C₃₇H₄₈N₆O₄S₂ 
• 1551453-99-6 C₂₉H₄₁N₇O₄S₂ 
• 1551454-03-5 C₃₆H₄₇N₇O₄S₂ 
• 1551455-46-9 C₂₄H₃₄N₄O₃S 
• 1551455-44-7 C₂₅H₃₆N₄O₄S 
• 155213-67-5 ritonavir 
• 176655-55-3 N-ritonavir 
• 1169870-34-1 C₃₆H₄₆N₆O₄S₂ 
• 1383570-15-7 tert-butyl [(2R,5R)-5-((S)-2-(3-((2-isopropylthiazol-4-yl)methyl)-3-methylureido)-3-methylbutanamido)-1,6-diphenylhexan-2-yl]carbamate 
• 1383570-28-2 C₃₈H₅₅N₅O₃S 
• 1383570-25-9 C₃₈H₅₆N₆O₃S 
• 1383570-23-7 C₃₆H₅₁N₅O₄S 
• 1383570-16-8 C₃₈H₄₉N₅O₄S₂ 
• 1383570-58-8 (S)-N-((2R,5R)-5-amino-1,6-diphenylhexan-2-yl)-2-(3-((2-isopropylthiazol-4-yl)methyl)-3-methylureido)-3-methylbutanamide hydrochloride 

Relevant articles and documents

Preparation method of ritonavir

The invention relates to the technical field of medicine, in particular to a preparation method of ritonavir. According to the preparation method of the ritonavir, (2-isopropyl thiazole-4-yl)-nitrogen-methyl methylamine is taken as a raw material, and the ritonavir is synthesized through a three-step reaction; a urea bond is built by trichloroethanol chloroformate, paratoluensulfonyl chloride which is cheap and easy to obtain is adopted as a condensing agent for amide, the ritonavir is synthesized with the high yield, and the yield of the ritonavir is 79%; and compared with an existing preparation method, the preparation method has the advantages of low cost, environment friendliness, easy scale production and the like, and has good application prospects.

Structure-activity relationships of diamine inhibitors of cytochrome P450 (CYP) 3A as novel pharmacoenhancers. Part II: P2/P3 region and discovery of cobicistat (GS-9350)

The HIV protease inhibitor (PI) ritonavir (RTV) has been widely used as a pharmacoenhancer for other PIs, which are substrates of cytochrome P450 3A (CYP3A). However the potent anti-HIV activity of ritonavir may limit its use as a pharmacoenhancer with other classes of anti-HIV agents. Ritonavir is also associated with limitations such as poor physicochemical properties. To address these issues a series of compounds with replacements at the P2 and/or P3 region was designed and evaluated as novel CYP3A inhibitors. Through these efforts, a potent and selective inhibitor of CYP3A, GS-9350 (cobicistat) with improved physiochemical properties was discovered.

MODULATORS OF PHARMACOKINETIC PROPERTIES OF THERAPEUTICS

The present application provides for a compound of Formula I, or a pharmaceutically acceptable salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods and include the administration of such compounds with at least one additional therapeutic agent.