2,4-Dichloro-5-(trifluoromethyl)pyrimidine → (R)-tert-butyl 1-(4-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate

HRID 886991노트

반응식

HRID 886991 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9])=[CH:4][CH:3]=1.Cl[C:19]1[N:24]=[C:23]([Cl:25])[C:22]([C:26]([F:29])([F:28])[F:27])=[CH:21][N:20]=1>ClCCCl.CC(O)(C)C.[Zn+2].[Br-].[Br-]>[Cl:25][C:23]1[C:22]([C:26]([F:28])([F:27])[F:29])=[CH:21][N:20]=[C:19]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9])=[CH:4][CH:3]=2)[N:24]=1

참가 물질

5

반응물 2

HCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 10633571(R)-[1-(4-Amino-phenyl)-ethyl]-carbamic acid tert-butyl ester

생성물 1

HCID 57584789(R)-tert-butyl 1-(4-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate

시약·촉매·용매 2

HCID 10421208Zinc bromide촉매HCID 21868497Tert-butyl alcohol 1,2-dichloroethane용매

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온도
25 °C

실험 절차

C2 (690 mg, 2.92 mmol) was dissolved in 10 mL DCE:t-BuOH (1:1 vol:vol), and the resultant solution was treated with ZnBr2 (1.97 g, 8.76 mmol) and 2,4-dichloro-5-(trifluoromethyl)pyrimidine (748 mg, 3.45 mmol). The resultant mixture was then treated drop-wise with TEA (406 ml, 2.92 mmol), and the mixture was allowed to stir at 25° C. for about 20 hours. The reaction mixture was concentrated, and the resultant residue was treated with EtOAc. The resultant solution was washed with water and brine, and dried over MgSO4. The mixture was then filtered, concentrated, and purified by column chromatography eluting with 22% EtOAc/Heptane. The product-containing eluents were combined and concentrated to provide C3 as a white solid. Yield: 680 mg, 56%. MS-415.2. 1H NMR (500 MHz, DMSO) δ: 10.59 (s, 1H), 8.74 (s, 1H), 7.53 (d, 2H), 7.31 (d, 1H), 7.23 (d, 2H), 4.54 (m, 1H), 1.33 (s, 9H), 1.25 (d, 3H).

후처리

  1. concentrationThe reaction mixture was concentrated
  2. additionthe resultant residue was treated with EtOAc
  3. washThe resultant solution was washed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationThe mixture was then filtered
  6. concentrationconcentrated
  7. custompurified by column chromatography
  8. washeluting with 22% EtOAc/Heptane
  9. concentrationconcentrated

출처 및 근거

ORD 기록
ord-7ec66e2ba0614454b9526e16d382e4ee
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08247411B2

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