1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-N-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1H-pyrrole-2-carboxamide

HRID 1964554ノート

反応式

HRID 1964554 の反応式
[CH3:1][O:2][CH2:3][C@H:4]([CH3:31])[O:5][C:6]1[CH:7]=[C:8]([C:23]2[NH:27][C:26]([C:28]([OH:30])=O)=[CH:25][CH:24]=2)[CH:9]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=2)[CH:11]=1.[NH2:32][CH2:33][C@H:34]([OH:39])[C:35]([F:38])([F:37])[F:36].CCN=C=NCCCN(C)C.Cl>CN(C)C1C=CN=CC=1.ClCCl>[CH3:1][O:2][CH2:3][C@H:4]([CH3:31])[O:5][C:6]1[CH:7]=[C:8]([C:23]2[NH:27][C:26]([C:28]([NH:32][CH2:33][C@H:34]([OH:39])[C:35]([F:38])([F:37])[F:36])=[O:30])=[CH:25][CH:24]=2)[CH:9]=[C:10]([O:12][C:13]2[CH:14]=[CH:15][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:17][CH:18]=2)[CH:11]=1

参加物

6

反応物 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2779001(2S)-3-amino-1,1,1-trifluoro-2-propanolHCID 666818155-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrole-2-carboxylic acid

生成物 1

HCID 666825025-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-N-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1H-pyrrole-2-carboxamide収率 67%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒2 回

実験手順

5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrole-2-carboxylic acid (408 mg, 0.94 mmol) synthesized in Example (18a), (2S)-3-amino-1,1,1-trifluoro-2-propanol (177 mg, 1.37 mmol) and 4-dimethylaminopyridine (224 mg, 1.87 mmol) were dissolved in dichloromethane (20 mL), and WSCI.HCl (193 mg, 1.01 mmol) was added at room temperature, followed by stirring for 2 hours under nitrogen atmosphere. The reaction solution was diluted with dichloromethane (200 mL), washed with 1N hydrochloric acid, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=50%-70%) to afford the desired product (339 mg, yield 67%) as a white amorphous substance.

後処理

  1. washwashed with 1N hydrochloric acid
  2. dry with materiala saturated aqueous sodium hydrogencarbonate solution and saturated brine, and subsequently dried over anhydrous magnesium sulfate
  3. distillationThe solvent was distilled off under reduced pressure
  4. customthe resulting residue was purified
  5. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=50%-70%)

出典と根拠

ORDレコード
ord-4689b91b195e420f82804675e74d835b
出典データセット
uspto-grants-2013_04
特許番号
US08415359B2

反応ノート

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