Phosphorus oxychloride → (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(imidazo[1,5-a]pyrazin-3-yl)propyl isoquinolin-3-ylcarbamate

HRID 409875노트

반응식

HRID 409875 반응식
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12](=[O:41])[O:13][CH2:14][C@@H:15]([N:27]([CH3:40])[C:28]([NH:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=2[Cl:39])=[O:29])[CH2:16][C:17](=O)[NH:18][CH2:19][C:20]2[CH:25]=[N:24][CH:23]=[CH:22][N:21]=2)[N:2]=1.P(Cl)(Cl)(Cl)=O>C(Cl)Cl>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12](=[O:41])[O:13][CH2:14][C@@H:15]([N:27]([CH3:40])[C:28]([NH:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=2[Cl:39])=[O:29])[CH2:16][C:17]2[N:21]3[CH:22]=[CH:23][N:24]=[CH:25][C:20]3=[CH:19][N:18]=2)[N:2]=1

참가 물질

4

반응물 2

HCID 24813Phosphorus oxychlorideHCID 57947597(S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4-oxo-4-(pyrazin-2-ylmethylamino)butyl isoquinolin-3-ylcarbamate

생성물 1

HCID 57947628(S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(imidazo[1,5-a]pyrazin-3-yl)propyl isoquinolin-3-ylcarbamate수율 43%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a mixture of (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4-oxo-4-(pyrazin-2-ylmethylamino)butyl isoquinolin-3-ylcarbamate (650 mg, 1.12 mmol) and DCM (50 mL) were added phosphoryl chloride (0.514 mL, 0.00561 mol). The resulting mixture was stirred at RT for overnight. The resulting solution was concentrated. The resulting residue was purified on prep-HPLC (ACN/H2O with 0.1% HCOOH) to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(imidazo[1,5-a]pyrazin-3-yl)propyl isoquinolin-3-ylcarbamate (0.27 g, 43%). LRMS (M+H+) m/z 562.1

후처리

  1. concentrationThe resulting solution was concentrated
  2. customThe resulting residue was purified on prep-HPLC (ACN/H2O with 0.1% HCOOH)

출처 및 근거

ORD 기록
ord-a456b3e2d93143bbad388d13b2f8ef16
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759374B2

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