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

HRID 2077063

Reaction equation

HRID 2077063 reaction equation
[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

Participants

5

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 10421208Zinc bromideCatalystHCID 21868497Tert-butyl alcohol 1,2-dichloroethaneSolvent

Conditions

Temperature
25 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-d399acda7f1b413597d5d9f225454820
Source dataset
uspto-grants-2011_04
Patent number
US07928109B2

Linked notes

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