Isopropanol → 2-[2-(3-Methoxy-5-methyl-6-oxo-5,6,8,9-tetrahydro-7-oxa-5-aza-benzocyclohepten-2-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-N-methyl-benzamide

HRID 1041509노트

반응식

HRID 1041509 반응식
Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[C:14]([O:26][CH3:27])=[CH:15][C:16]3[N:22]([CH3:23])[C:21](=[O:24])[O:20][CH2:19][CH2:18][C:17]=3[CH:25]=2)[N:3]=1.[NH2:28][C:29]1[CH:38]=[CH:37][CH:36]=[CH:35][C:30]=1[C:31]([NH:33][CH3:34])=[O:32].C(O)(C)C.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>>[CH3:27][O:26][C:14]1[C:13]([NH:12][C:4]2[N:3]=[C:2]([NH:28][C:29]3[CH:38]=[CH:37][CH:36]=[CH:35][C:30]=3[C:31]([NH:33][CH3:34])=[O:32])[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=2)=[CH:25][C:17]2[CH2:18][CH2:19][O:20][C:21](=[O:24])[N:22]([CH3:23])[C:16]=2[CH:15]=1

참가 물질

5

반응물 4

HCID 3776IsopropanolHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 3080722-Amino-N-methylbenzamideHCID 866340542-(4-Chloro-5-trifluoromethyl-pyrimidin-2-ylamino)-3-methoxy-5-methyl-8,9-dihydro-5H-7-oxa-5-aza-benzocyclohepten-6-one

생성물 1

HCID 668297652-[2-(3-Methoxy-5-methyl-6-oxo-5,6,8,9-tetrahydro-7-oxa-5-aza-benzocyclohepten-2-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-N-methyl-benzamide수율 29%

실험 절차

2-(4-Chloro-5-trifluoromethyl-pyrimidin-2-ylamino)-3-methoxy-5-methyl-8,9-dihydro-5H-7-oxa-5-aza-benzocyclohepten-6-one and 2-Amino-N-methyl-benzamide (85 mg, 0.56 mmol;) was stirred in isopropyl alcohol (5.00 mL, 65.3 mmol;) with 10-camphorsulfonic acid (150 mg, 0.63 mmol;) at 120° C. in microwave for 30 min×3. The reaction mixture was concentrated and then extracted with DCM (20 mL) and washed with sat. NaHCO3 (20 mL) followed by water. The organic layer was dried over MgSO4, filtered and concentrated. The residue was chromatographed on ISCO flash system (0-100% Hex:EtOAc) to obtain the product as one of multiple peaks by UV. The fractions were concentrated and triturated in Et2O to obtain a filterable solid (25 mg, 29%). mp: 210-212° C. (soft 150), MS (ESI+): 517 (M+H), 1H-NMR (CDCl3, 400 MHz) δ 10.85 (s, 1H), 8.42 (s, 1H), 8.40 (s, 1H), 8.24 (s, 1H), 7.71 (s, 1H), 7.52 (d, J=8 Hz, 1H), 7.43 (t, J=8 Hz, 1H), 7.13 (t, J=8 Hz, 1H), 6.70 (s, 1H), 6.19 (br s, 1H), 4.42 (t, J=6 Hz, 2H), 3.92 (s, 3H), 3.40 (s, 3H), 3.04 (d, J=5 Hz, 3H), 2.76 (t, 2H).

후처리

  1. concentrationThe reaction mixture was concentrated
  2. extractionextracted with DCM (20 mL)
  3. washwashed with sat. NaHCO3 (20 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed on ISCO flash system (0-100% Hex:EtOAc)
  8. customto obtain the product as one of multiple peaks by UV
  9. concentrationThe fractions were concentrated
  10. customtriturated in Et2O

출처 및 근거

ORD 기록
ord-ede1a49e47b34839bf4251fc1a8177f3
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08552186B2

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