Diisopropylethylamine → 2-Chloro-N-[3-(methylsulfonyl)benzyl]-5-(trifluoromethyl)pyrimidin-4-amine

HRID 511235

반응식

HRID 511235 반응식
C(N(C(C)C)CC)(C)C.[Cl:10][C:11]1[N:16]=[C:15](Cl)[C:14]([C:18]([F:21])([F:20])[F:19])=[CH:13][N:12]=1.Cl.[CH3:23][S:24]([C:27]1[CH:28]=[C:29]([CH2:33][NH2:34])[CH:30]=[CH:31][CH:32]=1)(=[O:26])=[O:25].ClC1C(C(F)(F)F)=CN=C(NCC2C=CC=C(S(C)(=O)=O)C=2)N=1>C1COCC1.C(Cl)Cl>[Cl:10][C:11]1[N:16]=[C:15]([NH:34][CH2:33][C:29]2[CH:30]=[CH:31][CH:32]=[C:27]([S:24]([CH3:23])(=[O:26])=[O:25])[CH:28]=2)[C:14]([C:18]([F:21])([F:20])[F:19])=[CH:13][N:12]=1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 447171423-(Methylsulfonyl)benzylamine hydrochlorideHCID 866540004-chloro-N-[3-(methylsulfonyl)benzyl]-5-(trifluoromethyl)pyrimidin-2-amine

생성물 1

HCID 866539992-Chloro-N-[3-(methylsulfonyl)benzyl]-5-(trifluoromethyl)pyrimidin-4-amine수율 38.7%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

Diisopropylethylamine (31.5 mL, 180 mmol) was added to a suspension of 2,4-dichloro-5-trifluoromethylpyrimidine (XL, 15.0 g, 69.4 mmol) and 1-[3-(methylsulfonyl)phenyl]methanamine hydrochloride (13.3 g, 60 mmol) in THF (300 mL) at 0° C., and the resulting mixture stirred at room temperature overnight. The mixture was then evaporated to dryness, the residue taken up in methylene chloride (100 mL) and the resulting solution washed with water (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue obtained was taken up in hot methylene chloride (35 mL) then left to stir overnight at room temperature. The separated solid was isolated by filtration (9.4 g) and determined to be a pure sample of the more polar component of the product mixture (4-chloro-N-[3-(methylsulfonyl)benzyl]-5-(trifluoromethyl)pyrimidin-2-amine XLIVb). The mother liquors were adsorbed onto silica gel and chromatographed over silica gel eluting with hexane:ethyl acetate 50:50 to afford 8.5 g of pure non-polar material (2-chloro-N-[3-(methylsulfonyl)benzyl]-5-(trifluoromethyl)pyrimidin-4-amine XLIVa) and a further 0.7 g of the polar component.

후처리

  1. customThe mixture was then evaporated to dryness
  2. washthe resulting solution washed with water (100 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue obtained
  7. waitthen left
  8. stirringto stir overnight at room temperature
  9. customThe separated solid was isolated by filtration (9.4 g)
  10. customchromatographed over silica gel eluting with hexane:ethyl acetate 50:50

출처 및 근거

ORD 기록
ord-3d42902f43394b35a55c197ca58a8dfd
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096624B2

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