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

HRID 655786ノート

反応式

HRID 655786 の反応式
[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]

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 594025744-chloro-3-cyano-5-methyl-1H-pyrrole-2-carboxylic acid2 回HCID 66707582ethyl (3R,4S)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-propoxypiperidine-1-carboxylate2 回

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e3b2685465044a7b8012eeaf7c06a864
出典データセット
uspto-grants-2011_12
特許番号
US08071605B2

反応ノート

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