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

HRID 886991Notes

Reaction equation

HRID 886991 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-7ec66e2ba0614454b9526e16d382e4ee
Source dataset
uspto-grants-2012_08
Patent number
US08247411B2

Reaction notes

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