Cyclohexanesulfonyl chloride → N-{3-[5-(2-Chloro-4-pyrimidinyl)-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}cyclohexanesulfonamide

HRID 239359

반응식

HRID 239359 반응식
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:19]2[C:20]([F:26])=[C:21]([CH:23]=[CH:24][CH:25]=2)[NH2:22])[CH:5]=[CH:4][N:3]=1.[CH:27]1([S:33](Cl)(=[O:35])=[O:34])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>N1C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[N:10][C:9]=2[C:19]2[C:20]([F:26])=[C:21]([NH:22][S:33]([CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)(=[O:35])=[O:34])[CH:23]=[CH:24][CH:25]=2)[CH:5]=[CH:4][N:3]=1

참가 물질

4

반응물 2

HCID 237554Cyclohexanesulfonyl chloride2회HCID 579897213-(5-(2-Chloropyrimidin-4-yl)-2-morpholinothiazol-4-yl)-2-fluoroaniline

생성물 1

HCID 57989819N-{3-[5-(2-Chloro-4-pyrimidinyl)-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}cyclohexanesulfonamide수율 37.2%

시약·촉매·용매 1

HCID 1049Pyridine용매

실험 절차

3-(5-(2-Chloropyrimidin-4-yl)-2-morpholinothiazol-4-yl)-2-fluoroaniline (200 mg, 0.510 mmol) was suspended in pyridine (2 mL) and after 5 min, cyclohexanesulfonyl chloride (0.148 mL 1.021 mmol) was added. The mixture was stirred overnight. Additional cyclohexanesulfonyl chloride (0.100 mL 0.69 mmol) was added and stirred overnight. Silica gel was added the reaction mixture and concentrated. The crude product was chromatographed on silica gel eluting with DCM and 9:1 (EtOAc:MeOH). The product was chromatographed again with 9:1 hexane:EtOAc increasing to 1:1 gradient. The clean fractions were concentrated to yield the title compound of Step A (102 mg, 37% yield). A second reaction was run (46 mg, 17% yield) same scale and combined to yield the title compound of Step A (148 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.70 (s, 1H) 8.34 (d, J=5.5 Hz, 1H) 7.55 (td, J=7.6, 2.0 Hz, 2H) 7.14-7.38 (m, 3H) 6.65 (d, J=5.5 Hz, 1H) 3.68 (t, J=4.7 Hz, 4H) 3.52 (t, J=4.6 Hz, 4H) 2.79-3.04 (m, 1H) 2.01 (d, J=11.4 Hz, 2H) 1.69 (d, J=13.0 Hz, 3H) 1.47-1.63 (m, 2H) 1.26-1.42 (m, 3H) 0.84 (t, J=7.4 Hz, 1H).

후처리

  1. stirringstirred overnight
  2. additionSilica gel was added the reaction mixture
  3. concentrationconcentrated
  4. customThe crude product was chromatographed on silica gel eluting with DCM and 9:1 (EtOAc:MeOH)
  5. customThe product was chromatographed again with 9:1 hexane
  6. concentrationThe clean fractions were concentrated

출처 및 근거

ORD 기록
ord-25bf658aa8af4f3485f80ff1cb361879
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08642759B2

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