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 2063463노트

반응식

HRID 2063463 반응식
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

참가 물질

8

반응물 5

HCID 81531Diisopropylethylamine2회HCID 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

생성물 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-carboxamide수율 174%

시약·촉매·용매 2

HCID 6344Dichloromethane용매3회HCID 57417360Sodium chloride; water용매

반응 조건

온도
0 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-c31f779cbfe747e7b7132c3d499bed73
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08288371B2

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