4-Methylmorpholine → Ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate

HRID 655758ノート

反応式

HRID 655758 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].[NH2:13][C@@H:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:16][C@@H:15]1[O:25][CH2:26][CH:27]=[CH2:28].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>ClCCl>[Cl:1][C:2]1[C:3]([C:11]#[N:12])=[C:4]([C:8]([NH:13][C@@H:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:16][C@@H:15]2[O:25][CH2:26][CH:27]=[CH2:28])=[O:10])[NH:5][C:6]=1[CH3:7]

参加物

7

反応物 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58075108Ethyl (3S,4R)-4-amino-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate2 回HCID 594025744-chloro-3-cyano-5-methyl-1H-pyrrole-2-carboxylic acid2 回

生成物 1

HCID 59402444Ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate収率 90.7%

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, 562 mg, 3.07 mmol) and ethyl (3S,4R)-4-amino-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate (Intermediate 18, 700 mg, 3.07 mmol) in dichloromethane (150 mL) were added HOBt (470 mg, 3.07 mmol) and N-methyl morpholine (1.01 mL, 9.21 mmol). The reaction mixture was stirred for 1 h at room temperature and EDC HCl (1.05 g, 5.52 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with the addition of 2 N HCl (100 mL). The organic layer was washed with sodium bicarbonate (150 mL), water (150 mL) and brine, and dried over anhydrous sodium sulphate, filtered, and concentrated under vacuum. Purification by column chromatography (silica, 35% ethyl acetate in pet ether) afforded Ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate 1.1 g (90%) as brown solid.

後処理

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature overnight
  3. customThe reaction mixture was quenched with the addition of 2 N HCl (100 mL)
  4. washThe organic layer was washed with sodium bicarbonate (150 mL), water (150 mL) and brine
  5. dry with materialdried over anhydrous sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customPurification by column chromatography (silica, 35% ethyl acetate in pet ether)

出典と根拠

ORDレコード
ord-100208ae946a43de8bb1e39567c7bfa6
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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