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

HRID 2063463ノート

反応式

HRID 2063463 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.Cl.[Cl:38][C:39]1[CH:56]=[CH:55][C:42]([CH2:43][N:44]2[C:48]([C@H:49]3[CH2:53][CH2:52][CH2:51][NH:50]3)=[N:47][N:46]=[C:45]2[Cl:54])=[CH:41][CH:40]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.[Cl-].[Na+].O>[Cl:38][C:39]1[CH:56]=[CH:55][C:42]([CH2:43][N:44]2[C:45]([Cl:54])=[N:46][N:47]=[C:48]2[C@H:49]2[CH2:53][CH2:52][CH2:51][N:50]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:41][CH:40]=1

参加物

8

反応物 5

HCID 81531Diisopropylethylamine2 回HCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 46911908(S)-7-(trifluoromethyl)chroman-4-amineHCID 68811430(R)-4-(4-chlorobenzyl)-3-chloro-5-(pyrrolidin-2-yl)-4H-1,2,4-triazole HCl salt

生成物 1

HCID 57650131(R)-2-(4-(4-chlorobenzyl)-5-chloro-4H-1,2,4-triazol-3-yl)-N-((S)-7-(trifluoromethyl)chroman-4-yl)pyrrolidine-1-carboxamide収率 174%

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 (14.87 mg, 0.05 mmol) in 8 mL of CH2Cl2 at 0° C. was added dropwise a mixed solution of (S)-7-(trifluoromethyl)chroman-4-amine (32.58 mg, 0.15 mmol) and N,N-diisopropylethylamine (0.07841 mL, 0.45 mmol) in dichloromethane (2 mL). The reaction mixture was stirred at 0° C. for 30 minutes. Then to the mixture at 0° C. was added a solution of (R)-4-(4-chlorobenzyl)-3-chloro-5-(pyrrolidin-2-yl)-4H-1,2,4-triazole HCl salt (50.05 mg, 0.15 mmol) and N,N-diisopropylethylamine (0.07841 mL, 0.45 mmol) in dichloromethane (2 mL) slowly. 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 as a brown oil (47 mg, 58.0%).

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-c31f779cbfe747e7b7132c3d499bed73
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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