Triethylamine → N-{3-[5-(3-methyl-5-{[4-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]oxetan-3-yl}methanesulfonamide

HRID 1040067노트

반응식

HRID 1040067 반응식
[NH2:1][C:2]1([C:6]2[S:7][C:8]([C:11]3[CH:12]=[C:13]([NH:18][C:19]4[N:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=4)[CH:14]=[C:15]([CH3:17])[CH:16]=3)=[CH:9][N:10]=2)[CH2:5][O:4][CH2:3]1.CCN(CC)CC.[CH3:36][S:37](Cl)(=[O:39])=[O:38]>ClCCl.C(OCC)(=O)C>[CH3:17][C:15]1[CH:16]=[C:11]([C:8]2[S:7][C:6]([C:2]3([NH:1][S:37]([CH3:36])(=[O:39])=[O:38])[CH2:3][O:4][CH2:5]3)=[N:10][CH:9]=2)[CH:12]=[C:13]([NH:18][C:19]2[N:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=2)[CH:14]=1

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 58456097N-{3-[2-(3-aminooxetan-3-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine

생성물 1

HCID 58456424N-{3-[5-(3-methyl-5-{[4-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]oxetan-3-yl}methanesulfonamide수율 47.5%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of N-{3-[2-(3-aminooxetan-3-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine (200 mg, 0.491 mmol) and Et3N (82 μL, 0.589 mmol) in dichloromethane (3.9 mL), methanesulfonyl chloride (57 μL, 0.736 mmol) was added. The reaction mixture was stirred at room temperature for 95 minutes. The mixture was then 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 (10-100% ethyl acetate in hexanes) and lyophilized to afford N-{3-[5-(3-methyl-5-{[4-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]oxetan-3-yl}methanesulfonamide (113 mg, 0.233 mmol, 47.4% yield) as a white powder. MS ESI: [M+H]+ m/z 486.0. 1H NMR (500 MHz, DMSO-d6) δ 10.28 (s, 1H), 8.83 (m, 2H), 8.11 (s, 1H), 7.99 (s, 1H), 7.50 (s, 1H), 7.29 (m, 1H), 7.21 (s, 1H), 4.91 (dd, J=6.6, 16.1, 4H), 2.98 (s, 3H), 2.33 (s, 3H). rhSYK activity=+++

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 (10-100% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-0a8392fbb82140ab8186a0292fe4ade3
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08551984B2

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