Diisopropylethylamine → (R)-2-(2-(4-chlorobenzyl)-5-methyl-2H-1,2,4-triazol-3-yl)-N-((S)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl)pyrrolidine-1-carboxamide

HRID 2063481ノート

反応式

HRID 2063481 の反応式
ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[F:13][C:14]([F:27])([F:26])[C:15]1[CH:24]=[C:23]2[C:18]([C@@H:19]([NH2:25])[CH2:20][CH2:21][O:22]2)=[CH:17][CH:16]=1.C(N(CC)C(C)C)(C)C.[N-:37]=[C:38]=[O:39].[Cl:40][C:41]1[CH:58]=[CH:57][C:44]([CH2:45][N:46]2[C:50]([C@H:51]3[CH2:55][CH2:54][CH2:53]N3)=[N:49][C:48]([CH3:56])=[N:47]2)=[CH:43][CH:42]=1>ClCCl>[Cl:40][C:41]1[CH:58]=[CH:57][C:44]([CH2:45][N:46]2[C:50]([C@H:51]3[CH2:55][CH2:54][CH2:53][N:37]3[C:38]([NH:25][C@@H:19]3[C:18]4[C:23](=[CH:24][C:15]([C:14]([F:13])([F:26])[F:27])=[CH:16][CH:17]=4)[O:22][CH2:21][CH2:20]3)=[O:39])=[N:49][C:48]([CH3:56])=[N:47]2)=[CH:43][CH:42]=1

参加物

7

反応物 5

HCID 81531Diisopropylethylamine2 回HCID 94429TriphosgeneHCID 105034IsocyanateHCID 46911908(S)-7-(trifluoromethyl)chroman-4-amineHCID 57650059(R)-1-(4-chlorobenzyl)-3-methyl-5-(pyrrolidin-2-yl)-1H-1,2,4-triazole

生成物 1

HCID 57650243(R)-2-(2-(4-chlorobenzyl)-5-methyl-2H-1,2,4-triazol-3-yl)-N-((S)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl)pyrrolidine-1-carboxamide収率 15%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

実験手順

To a stirring solution of triphosgene (18 mg, 0.06 mmol) in dichloromethane (3 ml) was slowly added dropwise via syringe a premixed solution of (S)-7-(trifluoromethyl)chroman-4-amine (39 mg, 0.18 mmol) and N,N-diisopropylethylamine (0.069 ml) dissolved in dichloromethane (3 ml). The reaction mixture was stirred at room temperature for 30 minutes. The isocyanate thereby generated was then treated dropwise with a solution of (R)-1-(4-chlorobenzyl)-3-methyl-5-(pyrrolidin-2-yl)-1H-1,2,4-triazole (52 mg, 0.18 mmol) and N,N-diisopropylethylamine (0.067 ml, 0.4 mmol) dissolved in dichloromethane (5 ml). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was evaporated to dryness, diluted with EtOAc, washed with 5% aqueous NaHCO3 and brine, dried (Na2SO4), filtered and concentrated. Purification by preparative HPLC yielded a clear oil (14 mg, 15%)

後処理

  1. stirringThe reaction mixture was stirred at room temperature for 16 h
  2. customThe reaction mixture was evaporated to dryness
  3. additiondiluted with EtOAc
  4. washwashed with 5% aqueous NaHCO3 and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by preparative HPLC

出典と根拠

ORDレコード
ord-fb594d5674e549a188718983c11056d9
出典データセット
uspto-grants-2012_10
特許番号
US08288371B2

反応ノート

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