Ammonium formate → N-{2-Chloro-3-[5-(4-pyrimidinyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]phenyl}-2,6-difluorobenzenesulfonamide

HRID 239316노트

반응식

HRID 239316 반응식
[Cl:1][C:2]1[C:7]([C:8]2[N:9]=[C:10]([CH:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[S:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[C:15](Cl)[N:14]=2)=[CH:6][CH:5]=[CH:4][C:3]=1[NH:26][S:27]([C:30]1[C:35]([F:36])=[CH:34][CH:33]=[CH:32][C:31]=1[F:37])(=[O:29])=[O:28].C([O-])=O.[NH4+]>CCOC(C)=O.CO.[OH-].[OH-].[Pd+2]>[Cl:1][C:2]1[C:7]([C:8]2[N:9]=[C:10]([CH:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[S:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][N:14]=2)=[CH:6][CH:5]=[CH:4][C:3]=1[NH:26][S:27]([C:30]1[C:35]([F:36])=[CH:34][CH:33]=[CH:32][C:31]=1[F:37])(=[O:28])=[O:29]

참가 물질

6

반응물 2

HCID 2723923Ammonium formateHCID 57989796N-{2-Chloro-3-[5-(2-chloro-4-pyrimidinyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]phenyl}-2,6-difluorobenzenesulfonamide

생성물 1

HCID 57990022N-{2-Chloro-3-[5-(4-pyrimidinyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]phenyl}-2,6-difluorobenzenesulfonamide수율 40.6%

시약·촉매·용매 3

HCID 9942167Palladium hydroxide촉매HCID 887Methanol용매HCID 8857Ethyl Acetate용매

반응 조건

온도
60 °C

실험 절차

To a solution of N-{2-chloro-3-[5-(2-chloro-4-pyrimidinyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]phenyl}-2,6-difluorobenzenesulfonamide (0.15 g, 0.26 mmol) and ammonium formate (0.17 g, 2.6 mmol) in EtOAc (7 mL) and MeOH (7 mL) was added 20% palladium hydroxide on carbon (0.17 g, 0.24 mmol). The reaction mixture was heated to 60° C. for 2 h. The palladium was filtered off using a nylon membrane. The filtrate was concentrated under vacuum to a crude yellow solid. The residue was purified by silica gel chromatography eluting 0-100% EtOAC/hexanes. The resulting solid was dissolved in DCM (5 mL) and hexanes added to afford the title compound as a pale yellow solid (58 mg, 38.3% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.85 (s, 1H), 9.11 (d, J=1.3 Hz, 1H), 8.57 (d, J=5.4 Hz, 1H), 7.60-7.73 (m, 1H), 7.52-7.55 (m, 1H), 7.49 (t, J=7.7 Hz, 1H), 7.41-7.45 (m, 1H), 7.20 (t, J=9.1 Hz, 2H), 6.56 (dd, J=5.4, 1.3 Hz, 1H), 3.92 (ddd, J=9.6, 2.0, 1.9 Hz, 2H), 3.46 (td, J=11.6, 1.9 Hz, 2H), 2.00 (dd, J=12.8, 1.9 Hz, 2H), 1.68-1.80 (m, 2H), *Note: The methine (—H) peak of the THP (tetrahydro-2H-pyran-4-yl) group is submerged under the water peak at 3.33 ppm causing broadening. MS (ESI) 549.1 [M+H]+.

후처리

  1. filtrationThe palladium was filtered off
  2. concentrationThe filtrate was concentrated under vacuum to a crude yellow solid
  3. customThe residue was purified by silica gel chromatography
  4. washeluting 0-100% EtOAC/hexanes
  5. dissolutionThe resulting solid was dissolved in DCM (5 mL)
  6. additionhexanes added

출처 및 근거

ORD 기록
ord-231793f753784ecf88258043cfce2dac
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08642759B2

반응 노트

불러오는 중…