4-Methylmorpholine → ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-propoxypiperidine-1-carboxylate

HRID 655786노트

반응식

HRID 655786 반응식
[Cl:1][C:2]1[C:3]([C:11]#[N:12])=[C:4]([C:8]([OH:10])=O)[NH:5][C:6]=1[CH3:7].ClC1C=C(C([NH:22][C@H:23]2[CH2:28][CH2:27][N:26]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][C@H:24]2[O:34][CH2:35][CH2:36][CH3:37])=O)NC=1C.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>ClCCl>[Cl:1][C:2]1[C:3]([C:11]#[N:12])=[C:4]([C:8]([NH:22][C@@H:23]2[CH2:28][CH2:27][N:26]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][C@@H:24]2[O:34][CH2:35][CH2:36][CH3:37])=[O:10])[NH:5][C:6]=1[CH3:7]

참가 물질

6

반응물 4

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 594025744-chloro-3-cyano-5-methyl-1H-pyrrole-2-carboxylic acid2회HCID 66707582ethyl (3R,4S)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-propoxypiperidine-1-carboxylate2회

생성물 1

HCID 59402480ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-propoxypiperidine-1-carboxylate수율 76%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 4-chloro-3-cyano-5-methyl-1H-pyrrole-2-carboxylic acid (Intermediate 16, 2 g, 8.69 mmol) and ethyl (3S,4R)-4-amino-3-propoxypiperidine-1-carboxylate (see Intermediate 73, 1.59 g, 8.695 mmol) in dichloromethane (150 mL) was added N-Hydroxybenzotriazole (1.6 g, 10.43 mM) and N-methylmorpholine (2.63 g, 26.08 mmol). The reaction mixture was stirred for 1 h at room temperature and 1-Ethyl-3-(3-dimethyl amino propyl)carbodiimide hydrochloride (2.87 g, 15.6 mM) was added. The resulting reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with 2N hydrochloric acid (50 mL) and the layers were separated. The organic layer was washed with sodium bicarbonate (40 mL), water (60 mL) and finally with brine successively and dried over anhydrous sodium sulphate, filtered, concentrated under vacuum to afford ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-propoxypiperidine-1-carboxylate 2.6 g (76%) as solid.

후처리

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature overnight
  3. customThe reaction mixture was quenched with 2N hydrochloric acid (50 mL)
  4. customthe layers were separated
  5. washThe organic layer was washed with sodium bicarbonate (40 mL), water (60 mL) and finally with brine successively
  6. dry with materialdried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum

출처 및 근거

ORD 기록
ord-e3b2685465044a7b8012eeaf7c06a864
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08071605B2

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