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Trifluoroacetic acid → 4-Hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-1-sulfonamide

HRID 410562
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HRID 410562 반응식
C(OC(=O)[NH:7][S:8]([N:11]1[CH2:16][CH2:15][C:14]([OH:40])([C:17]2[S:18][C:19]([C:22]3[CH:27]=[C:26]([NH:28][C:29]4[N:34]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:32]=[CH:31][N:30]=4)[CH:25]=[C:24]([CH3:39])[CH:23]=3)=[CH:20][N:21]=2)[CH2:13][CH2:12]1)(=[O:10])=[O:9])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:40][C:14]1([C:17]2[S:18][C:19]([C:22]3[CH:27]=[C:26]([NH:28][C:29]4[N:34]=[C:33]([C:35]([F:36])([F:38])[F:37])[CH:32]=[CH:31][N:30]=4)[CH:25]=[C:24]([CH3:39])[CH:23]=3)=[CH:20][N:21]=2)[CH2:15][CH2:16][N:11]([S:8]([NH2:7])(=[O:9])=[O:10])[CH2:12][CH2:13]1
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참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acid2회HCID 58456421Tert-butyl({4-hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-phenyl)-1,3-thiazol-2-yl]piperidin-1-yl}sulfonyl)carbamate

생성물 1

HCID 584562224-Hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-1-sulfonamide수율 82.2%

시약·촉매·용매 1

HCID 6344Dichloromethane
용매

실험 절차

To a solution of tert-butyl({4-hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidin-1-yl}sulfonyl)carbamate (45 mg, 0.073 mmol) in DCM (0.7 mL) was added TFA (0.120 mL, 1.5 mmol) and the reaction was stirred at room temperature for 80 min, then more TFA (0.120 mL, 1.5 mmol) was added. After 90 min most volatiles were removed by N2 flow and vacuum. The residue was diluted with saturated aqueous NaHCO3 and ethyl acetate. The combined organic layers were dried and evaporated to give 4-hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-1-sulfonamide (31 mg, 0.06 mmol, 82% yield). MS ESI: [M+H]+ m/z 515.2. 1H NMR (600 MHz, CDCl3): δ 8.59 (d, J=4.8 Hz, 1H); 7.87 (s, 1H); 7.81 (s, 1H); 7.25 (s, 1H); 7.02 (s, 1H); 7.00 (d, J=4.8 Hz, 1H); 3.59 (d, J=12 Hz, 2H); 3.14 (m, 2H); 2.34 (s, 3H); 2.26 (m, 2H); 1.94 (d, J=12 Hz, 2H). rhSYK activity=+++

후처리

  1. customAfter 90 min most volatiles were removed by N2 flow and vacuum
  2. additionThe residue was diluted with saturated aqueous NaHCO3 and ethyl acetate
  3. customThe combined organic layers were dried
  4. customevaporated

출처 및 근거

ORD 기록
ord-6294a8f0558242a8b0d0816283a60fc6
출처 데이터셋
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08759366B2

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