(S)-Methyl (1-((4-(3-(5-chloro-2-fluoro-3-(N-(Methylsulfonyl)MethylsulfonaMido)phenyl)-1-isopropyl-1H-pyrazol-4-yl)pyriMidin-2-yl)aMino)propan-2-yl)carbaMate synthesis

15synthesis methods

Product Name:(S)-Methyl (1-((4-(3-(5-chloro-2-fluoro-3-(N-(Methylsulfonyl)MethylsulfonaMido)phenyl)-1-isopropyl-1H-pyrazol-4-yl)pyriMidin-2-yl)aMino)propan-2-yl)carbaMate
CAS Number:1269440-99-4
Molecular formula:C23H29ClFN7O6S2
Molecular Weight:618.1011

CarbaMic acid, N-[(1S)-2-[[4-[3-(3-aMino-5-chloro-2-fluorophenyl)-1-(1-Methylethyl)-1H-pyrazol-4-yl]-2-pyriMidinyl]aMino]-1-Methylethyl]-, Methyl ester

1269440-78-9
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124-63-0
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(S)-Methyl (1-((4-(3-(5-chloro-2-fluoro-3-(N-(Methylsulfonyl)MethylsulfonaMido)phenyl)-1-isopropyl-1H-pyrazol-4-yl)pyriMidin-2-yl)aMino)propan-2-yl)carbaMate

1269440-99-4
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Yield:-

Reaction Conditions:

Stage #1: methyl N-[(2S)-1-({4-[3-(5-chloro-2-fluoro-3-aminophenyl)isopropyl-1H-pyrazol-4-yl]pyrimidin-2-yl}amino)propan-2-yl]carbamate;methanesulfonyl chloridewith triethylamine in 2-methyltetrahydrofuran at -5 - 20;
Stage #2: with hydrogenchloride in 2-methyltetrahydrofuran;lithium hydroxide monohydrate; pH=6 - 6.5;
Stage #3: in 2-methyltetrahydrofuran;lithium hydroxide monohydrate at 20; pH=7 - 7.5; for 0.166667 h;

Steps:

6.19

Step 19. (S)-Methyl l-(4-(3-(5-chloro-2-fluoro-3-(N-(methylsulfonyl)methylsulfonamido)phenyl)-l-isopropyl-lH-pyrazol-4-yl)pyrimidin-2- ylamino)propan-2-ylcarbamate. To a flask was charged (S)-methyl l-(4-(3-(3-amino-5-chloro- 2-fluorophenyl)-l-isopropyl-lH-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate (-3.8 L methylTHF solution, -396.5 g, 0.86 mol) at 20 ⁰C. To the solution was added triethylamine ( 435.0 g, 4.3 mol). The solution was cooled to 0 to -5 ⁰C. To the solution was added methanesulfonyl chloride (246.0 g, 2.15 mol) dropwise with stirring over 20 min at 0 to -5 ⁰C. The mixture was allowed to warm to 18-20 ⁰C and was held at this temperature for 20 min. To the reaction mixture was added water ( 2115 mL) over 30 min at 18-20 ⁰C. The mixture was stirred 10 min at 20 ⁰C after the addition was complete. Then the pH was adjusted to between 6.0 and 6.5 with 2N HCl (-1230 mL). The pH was then adjusted to 7 - 7.5 using saturated aqueous sodium bicarbonate solution. The mixture was stirred 10 min (at) 20 ⁰C. The layers were separated. The 2-methylTHF layer containing the title compound was used directly in step 20.

References:

WO2011/25927,2011,A1 Location in patent:Page/Page column 68

1229025-89-1 Synthesis