98548-81-3

Basic information

• Product Name: (E)-4-(diMethylaMino)but-2-enoic acid
• Synonyms: (E)-4-(diMethylaMino)but-2-enoic acid;4-(DiMethylaMino)-2-butenoic acid hydrochloride;4-Dimethylaminobut-2-enoic acid hydrochloride;4-(Dimethylamino)-2-butenoic acid hydrochloride 97%;4-Dimethylaminobuten2oic acid,HCIp,2-Butenoic acid,4-(dimethylamino)-,HCL
• CAS NO: 98548-81-3
• Molecular Formula: C₆H₁₁NO₂*ClH
• Molecular Weight: 129.15704
• Mol File: 98548-81-3.mol
• Article Data: 5

Chemical Properties

• Melting Point: 225-229℃
• Appearance: /
• Storage Temp.: Inert atmosphere,Room Temperature
• CAS DataBase Reference: (E)-4-(diMethylaMino)but-2-enoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (E)-4-(diMethylaMino)but-2-enoic acid(98548-81-3)
• EPA Substance Registry System: (E)-4-(diMethylaMino)but-2-enoic acid(98548-81-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 98548-81-3(Hazardous Substances Data)

Synthetic route

methyl 4-(dimethylamino)but-2-enoate hydrochloride → trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3)

Conditions	Yield
With hydrogenchloride In water for 6h; Reflux;	98%

ethyl 4-(dimethylamino)crotonate (98552-51-3) → trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3)

Conditions	Yield
Stage #1: ethyl 4-(dimethylamino)crotonate With water; sodium hydroxide In ethanol at 0.25 - 0.55℃; for 0.1h; Stage #2: With hydrogenchloride In ethanol at 5℃; pH=1.5;	63%

4-bromocrotonic acid (13991-36-1, 20629-35-0) + dimethyl amine (124-40-3) → trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3)

Conditions	Yield
Stage #1: 4-bromocrotonic acid; dimethyl amine In tetrahydrofuran at 0℃; for 0.5h; Stage #2: With hydrogenchloride In water; isopropyl alcohol pH=2 - 3;	36%

4-dimethylaminocrotonic acid methyl ester hydrochloride (1259519-60-2) → trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3)

Conditions	Yield
With hydrogenchloride; sodium hydroxide In ethanol; isopropyl alcohol; acetone

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + 3-cyano-6-amino-7-ethoxy-4-(3-ethynylanilino)quinoline (1246087-09-1) → C26H25N5O2

Conditions	Yield
Stage #1: trans-4-dimethylaminocrotonic acid hydrochloride With oxalyl dichloride In tetrahydrofuran; N,N-dimethyl-formamide at 10 - 20℃; for 1h; Large scale; Stage #2: 3-cyano-6-amino-7-ethoxy-4-(3-ethynylanilino)quinoline In tetrahydrofuran; 1-methyl-pyrrolidin-2-one; N,N-dimethyl-formamide at -20 - 0℃; for 1h; Temperature; Large scale;	99.1%

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + (R)-5-fluoro-4’-((R)-3-(methoxymethyl)piperazin-1-yl)-2’-(((R)-1-methylpyrrolidin-2-yl)methoxy)-3,4,5,8’-tetrahydro-1H,6’H-spiro[naphthalene-2,7’-quinazoline] → (E)-4-(dimethylamino)-1-((R)-4-((R)-5-fluoro-2’-(((S)-1-methylpyrrolidin-2-yl)methoxy)-3,4,5’,8’-tetrahydro-1H,6’H-spiro[naphthalene-2,7’-quinazolin]-4’-yl)-2-(methoxymethyl)piperazin-1-yl)but-2-en-1-one

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In acetonitrile for 0.25h;	92%

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + 2-((S)-4-((S)-5-fluoro-2’-(((S)-1-methylpyrrolidin-2-yl)methoxy)-3,4,5’,8’-tetrahydro-1H,6’H-spiro[naphthalene-2,7’-quinazolin]-4’-yl)piperazin-2-yl)acetonitrile → 2-((S)-1-((E)-4-(dimethylamino)but-2-enoyl)-4((S)-5-fluoro-2’-(((S)-1-methylpyrrolidin-2-yl)methoxy)-3,4,5’,8’-tetrahydro-1H,6’H-spiro[naphthalene-2,7’-quinazolin]-4’-yl)piperazin-2-yl)acetonitrile

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 16h;	78%

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + phenethylamine (64-04-0) → 4-(dimethylamino)-N-phenethylbut-2-enamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at -20 - 20℃; Inert atmosphere;	73%

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + N-(6-amino-pyridin-2-yl)-N'-(3-chloro-4-fluorophenyl)-pyrimidine-4,6-diamine (1144561-28-3) → (E)-N-[6-(3-chloro-4-fluorophenylamino)pyrimidin-4-ylaminopyridin-2-yl]-4-(dimethylamino)but-2-enamide (1144561-29-4)

Conditions	Yield
Stage #1: trans-4-dimethylaminocrotonic acid hydrochloride With oxalyl dichloride; N,N-dimethyl-formamide In tetrahydrofuran at 0 - 20℃; for 2.5h; Stage #2: N-(6-amino-pyridin-2-yl)-N'-(3-chloro-4-fluorophenyl)-pyrimidine-4,6-diamine In tetrahydrofuran; 1-methyl-pyrrolidin-2-one at 0 - 20℃; for 2h;	69%

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + 4-{[6-(amino)quinolin-4-yl]oxy}-N-(pyridin-2-yl)benzamide → 4-[6-{[(2E)-4-dimethylaminobut-2-enoyl]amino}quinolin-4-yl]oxy-N-(pyridin-2-yl)benzamide

Conditions	Yield
With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 0℃; for 3h;	61%

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + C22H23N7O → N-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)-4-(dimethylamino)but-2-enamide

Conditions	Yield
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 1.5h;	40%

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + C12H14F3NO2 → C18H23F3N2O3

Conditions	Yield
Stage #1: trans-4-dimethylaminocrotonic acid hydrochloride With thionyl chloride In 1-methyl-pyrrolidin-2-one at 0℃; for 1h; Stage #2: C12H14F3NO2 With dmap; N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 20℃;	21%

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) → 4-N,N-dimethylaminocrotonoylchloride Hydrochloride (501332-27-0)

Conditions	Yield
With oxalyl dichloride; N,N-dimethyl-formamide In tetrahydrofuran at 0 - 20℃; for 3h;
With oxalyl dichloride In acetonitrile at 0 - 45℃; for 2.58333h;
With oxalyl dichloride In N,N-dimethyl-formamide at 0 - 30℃; for 2h; Reagent/catalyst; Solvent; Temperature;

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + (S)-5-((3,5-dimethoxyphenyl)ethynyl)-7-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine → (S)-1-(3-(4-amino-5-((3,5-dimethoxyphenyl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidin-1-yl)-4-(dimethylamino)but-2-en-1-one

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.0833333h;	3.9 mg
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.0833333h;	3.9 mg

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + (S)-3-((3,5-dimethoxyphenyl)ethynyl)-1-(pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine → (S)-1-(3-(4-amino-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)-4-(dimethylamino)but-2-en-1-one

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide	2.3 mg
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide	2.3 mg

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + C9H11IN6 → (S)-1-(3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)-4-(dimethylamino)but-2-en-1-one

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide	458 mg

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + 1-(azetidin-3-yl)-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine → 1-(3-{4-amino-3-[2-(3,5-dimethoxyphenyl)ethynyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl}azetidin-1-yl)-4-(dimethylamino)but-2-en-1-one

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + 6-amino-7-ethoxy-4-((4-phenoxyphenyl)amino)quinoline-3-carbonitrile → (E)-N-(3-cyano-7-ethoxy-4-((4-phenoxyphenyl)amino)quinolin-6-yl)-4-(dimethylamino)but-2-enamide

Conditions	Yield
Stage #1: trans-4-dimethylaminocrotonic acid hydrochloride With oxalyl dichloride In tetrahydrofuran; N,N-dimethyl-formamide at 5 - 20℃; for 3h; Stage #2: 6-amino-7-ethoxy-4-((4-phenoxyphenyl)amino)quinoline-3-carbonitrile In tetrahydrofuran; 1-methyl-pyrrolidin-2-one; N,N-dimethyl-formamide	1.56 g

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + 6-amino-4-((4-phenoxyphenyl)amino)quinoline-3-carbonitrile → (E)-N-(3-cyano-4-((4-phenoxyphenyl)amino)quinolin-6-yl)-4-(dimethylamino)but-2-enamide

Conditions	Yield
Stage #1: trans-4-dimethylaminocrotonic acid hydrochloride With oxalyl dichloride In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 3h; Cooling with ice; Stage #2: 6-amino-4-((4-phenoxyphenyl)amino)quinoline-3-carbonitrile In tetrahydrofuran; 1-methyl-pyrrolidin-2-one; N,N-dimethyl-formamide at 20℃; for 4h; Cooling with ice;	39 mg

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + 4-{[6-(amino)quinolin-4-yl]oxy}-N-(4-ethylpyridin-2-yl)benzamide → 4-[(6-{[(2E)-4-dimethylaminobut-2-enoyl]amino}quinolin-4-yl)oxy]-N-(4-ethylpyridin-2-yl)benzamide

Conditions	Yield
Stage #1: trans-4-dimethylaminocrotonic acid hydrochloride With oxalyl dichloride; N,N-dimethyl-formamide In acetonitrile at 60℃; for 0.5h; Stage #2: 4-{[6-(amino)quinolin-4-yl]oxy}-N-(4-ethylpyridin-2-yl)benzamide In 1-methyl-pyrrolidin-2-one; acetonitrile at 0 - 20℃;	22 mg

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + (S)-tert-butyl 3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidine-1-carboxylate → (S)-1-(3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)-4-(dimethylamino)but-2-en-1-one

Conditions	Yield
Stage #1: tert-butyl (S)-3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidine-1-carboxylate With hydrogenchloride In 1,4-dioxane for 1h; Stage #2: trans-4-dimethylaminocrotonic acid hydrochloride With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) → C21H19ClF3N5O2

Conditions	Yield
Multi-step reaction with 2 steps 1: oxalyl dichloride; N,N-dimethyl-formamide / tetrahydrofuran / 3 h / 0 - 20 °C 2: tetrahydrofuran / 0 - 20 °C View Scheme

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) → (E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(3-methoxypropoxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide

Conditions	Yield
Multi-step reaction with 2 steps 1: oxalyl dichloride / tetrahydrofuran; N,N-dimethyl-formamide / 0.5 h / 20 °C / Inert atmosphere 2: tetrahydrofuran; 1-methyl-pyrrolidin-2-one / 1 h View Scheme

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) → trans-4-dimethylamino crotonic acid chloride hydrochloride salt (1055943-40-2)

Conditions	Yield
With oxalyl dichloride In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 0.5h; Inert atmosphere;

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) → (E)-4-(dimethylamino)-N-(3-(5-fluoro-4-(m-tolylamino)pyrimidin-2-ylamino)phenyl)but-2-enamide (1202755-89-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: oxalyl dichloride / acetonitrile / 2.58 h / 0 - 45 °C 2: 1-methyl-pyrrolidin-2-one / 1 h / 0 - 10 °C View Scheme

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) → 4-(N,N-dimethylamino)-2-ene-butyryl chloride (774534-34-8)

Conditions	Yield
With oxalyl dichloride In tetrahydrofuran; N,N-dimethyl-formamide at 0 - 20℃; for 2h;
With oxalyl dichloride; N,N-dimethyl-formamide In tetrahydrofuran at 0 - 20℃; for 1.5h;	130 mg

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) → C27H29N3O5

Conditions	Yield
Multi-step reaction with 2 steps 1: oxalyl dichloride / N,N-dimethyl-formamide; tetrahydrofuran / 2 h / 0 - 20 °C 2: triethylamine / dichloromethane / 12 h / 20 °C View Scheme

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + 2-(4-phenoxyphenyl)-5,6,7,8-tetrahydro-4H-pyrazolo[5',1':2,3]imidazo[4,5-c]pyridine-3-carboxamide trifluoroacetate → 7-(4-(dimethylamino)but-2-enoyl)-2-(4-phenoxyphenyl)-5,6,7,8-tetrahydro-4H-pyrazolo[5',1':2,3]imidazo[4,5-c]pyridine-3-carboxamide

Conditions

Yield

Stage #1: trans-4-dimethylaminocrotonic acid hydrochloride; 2-(4-phenoxyphenyl)-5,6,7,8-tetrahydro-4H-pyrazolo[5',1':2,3]imidazo[4,5-c]pyridine-3-carboxamide trifluoroacetate With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 2h; Inert atmosphere; Stage #2: In dichloromethane at 20℃; Inert atmosphere;

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + 3-(1H-indazol-3-yl)aniline → C19H20N4O

Conditions	Yield
Stage #1: trans-4-dimethylaminocrotonic acid hydrochloride With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide; acetonitrile for 0.0833333h; Stage #2: 3-(1H-indazol-3-yl)aniline In N,N-dimethyl-formamide; acetonitrile at 20℃; for 48h; pH=8 - 9;

trans-4-dimethylaminocrotonic acid hydrochloride (98548-81-3) + phenethylamine (64-04-0) → N-ethyl-N,N-dimethyl-4-oxo-4-(phenethylamino)but-2-en-1-aminium

Conditions	Yield
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / -20 - 20 °C / Inert atmosphere 2.1: triethylamine; trimethylsilyl bromide / acetonitrile / 24 h / 36 °C / Inert atmosphere 2.2: 0.08 h / Inert atmosphere View Scheme

Upstream product

• 1413945-87-5 dimethylaminoacetaldehyde-hydrogen sulphite adduct 
• 88738-78-7 bis-(2,2,2-trifluoroethyl)(methoxycarbonylmethyl)phosphonate 
• 13991-36-1 4-bromocrotonic acid 
• 124-40-3 dimethyl amine 
• 98552-51-3 ethyl 4-(dimethylamino)crotonate 
• 1259519-60-2 4-dimethylaminocrotonic acid methyl ester hydrochloride 

Downstream Products

• 1055943-40-2 trans-4-dimethylamino crotonic acid chloride hydrochloride salt 
• 1202755-89-2 (E)-4-(dimethylamino)-N-(3-(5-fluoro-4-(m-tolylamino)pyrimidin-2-ylamino)phenyl)but-2-enamide 
• 1144561-29-4 (E)-N-[6-(3-chloro-4-fluorophenylamino)pyrimidin-4-ylaminopyridin-2-yl]-4-(dimethylamino)but-2-enamide 

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