1,4-Dioxane → N-{3-[2-(3-aminooxetan-3-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine

HRID 410576노트

반응식

HRID 410576 반응식
CC(S([NH:7][C:8]1([C:12]2[S:13][C:14]([C:17]3[CH:22]=[C:21]([NH:23][C:24]4[N:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][N:25]=4)[CH:20]=[C:19]([CH3:34])[CH:18]=3)=[CH:15][N:16]=2)[CH2:11][O:10][CH2:9]1)=O)(C)C.O1CCOCC1>CO.Cl.C(OCC)(=O)C>[NH2:7][C:8]1([C:12]2[S:13][C:14]([C:17]3[CH:22]=[C:21]([NH:23][C:24]4[N:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][N:25]=4)[CH:20]=[C:19]([CH3:34])[CH:18]=3)=[CH:15][N:16]=2)[CH2:9][O:10][CH2:11]1

참가 물질

6

반응물 2

HCID 312751,4-DioxaneHCID 672573262-methyl-N-{3-[5-(3-methyl-5-[[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]oxetan-3-yl]propane-2-sulfinamide

생성물 1

HCID 58456097N-{3-[2-(3-aminooxetan-3-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine수율 53.5%

시약·촉매·용매 3

HCID 313Hydrochloric Acid용매HCID 887Methanol용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution the product of Step 2 (1.01 g, 1.964 mmol) in methanol (9.8 mL), 4M HCl in Dioxane (1.97 mL, 7.86 mmol) was added. The mixture was stirred at room temperature for 15 minutes. The mixture was diluted with ethyl acetate, washed with saturated NaHCO3, followed by brine, dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography on silica (40-100% ethyl acetate in hexanes) to afford N-{3-[2-(3-aminooxetan-3-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine (386.6 mg, 0.954 mmol, 53.5% yield) as a pale yellow solid. MS ESI: [M+H]+ m/z 408.0. 1H NMR (500 MHz, DMSO-d6) δ 10.26 (s, 1H), 8.83 (d, J=4.8, 1H), 8.07 (s, 1H), 7.97 (s, 1H), 7.47 (s, 1H), 7.28 (d, J=4.9, 1H), 7.17 (s, 1H), 4.87 (d, J=5.6, 2H), 4.58 (d, J=5.7, 2H), 2.32 (s, 3H).

후처리

  1. washwashed with saturated NaHCO3
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography on silica (40-100% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-bad4cb84b5b84cc28bbcd786525dc8f4
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759366B2

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