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

HRID 2063458ノート

反応式

HRID 2063458 の反応式
Cl[C:2](Cl)([O:4]C(=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.OC(C(F)(F)F)=O.[Cl:44][C:45]1[CH:61]=[CH:60][C:48]([CH2:49][N:50]2[CH:54]=[N:53][N:52]=[C:51]2[C@H:55]2[CH2:59][CH2:58][CH2:57][NH:56]2)=[CH:47][CH:46]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.[Cl-].[Na+].O>[Cl:44][C:45]1[CH:61]=[CH:60][C:48]([CH2:49][N:50]2[CH:54]=[N:53][N:52]=[C:51]2[C@H:55]2[CH2:59][CH2:58][CH2:57][N:56]2[C:2]([NH:25][C@@H:19]2[C:18]3[C:23](=[CH:24][C:15]([C:14]([F:13])([F:26])[F:27])=[CH:16][CH:17]=3)[O:22][CH2:21][CH2:20]2)=[O:4])=[CH:47][CH:46]=1

参加物

8

反応物 5

HCID 81531Diisopropylethylamine2 回HCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 46911908(S)-7-(trifluoromethyl)chroman-4-amineHCID 86629195(R)-4-(4-chlorobenzyl)-3-(pyrrolidin-2-yl)-4H-1,2,4-triazole TFA salt

生成物 1

HCID 57650035(R)-2-(4-(4-chlorobenzyl)-4H-1,2,4-triazol-3-yl)-N-((S)-7-(trifluoromethyl)chroman-4-yl)pyrrolidine-1-carboxamide収率 52.6%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒3 回HCID 57417360Sodium chloride; water溶媒

反応条件

温度
0 °C

実験手順

To a stirring solution of triphosgene (0.0205 g, 0.691 mmol) in 8 mL of CH2Cl2 at 0° C. was added dropwise a mixed solution of (S)-7-(trifluoromethyl)chroman-4-amine (44.91 mg, 0.2068 mmol) and N,N-diisopropylethylamine (0.108 mL, 0.620 mmol) in dichloromethane (2 mL). The reaction mixture was stirred at 0° C. for 30 minutes. Then to the mixture at 0° C. was slowly added a solution of the (R)-4-(4-chlorobenzyl)-3-(pyrrolidin-2-yl)-4H-1,2,4-triazole TFA salt (0.125 g, 0.2068 mmol) and N,N-diisopropylethylamine (0.108 mL, 0.620 mmol) in dichloromethane (2 mL). The resulting mixture was stirred 0° C. for 30 minutes, then at room temperature overnight. The reaction mixture was treated with sat. aqueous NaHCO3 (10 mL) and brine, dried over Na2SO4, and concentrated in vacuo. Flash chromatography purification (Hex/EtOAc gradient, 10-100% EtOAc with 10% of MeOH) afforded the desired product (55 mg, 52.6%).

後処理

  1. stirringThe resulting mixture was stirred 0° C. for 30 minutes
  2. customat room temperature
  3. customovernight
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customFlash chromatography purification (Hex/EtOAc gradient, 10-100% EtOAc with 10% of MeOH)

出典と根拠

ORDレコード
ord-bd40fc2f7c7d4283a8813b0103b154fb
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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