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[CH:25]=[CH:24][C:16]([CH2:17][CH2:18][PH:19](=[O:23])[O:20][CH2:21][CH3:22])=[CH:15][CH:14]=2)[N:3]=1.[NH2:26][C:27]1[CH:28]=[CH:29][C:30]([Br:38])=[C:31]2[C:35]=1[C:34](=[O:36])[N:33]([CH3:37])[CH2:32]2.C(O)(C(F)(F)F)=O>>[Br:38][C:30]1[CH:29]=[CH:28][C:27]([NH:26][C:2]2[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]3[CH:25]=[CH:24][C:16]([CH2:17][CH2:18][PH:19](=[O:23])[O:20][CH2:21][CH3:22])=[CH:15][CH:14]=3)[N:3]=2)=[C:35]2[C:31]=1[CH2:32][N:33]([CH3:37])[C:34]2=[O:36]참가 물질
실험 절차
A solution of ethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)methylphosphinate (230 mg, 584 mmol) and 7-amino-4-bromo-2-methyl-2,3-dihydro-1H-isoindol-1-one (169 mg, 701 mmol) in TFE (2.0 mL) was charged with TFA (200 mg, 1.75 mmol) and the reaction mixture irradiated in a microwave reactor at 105° C. for 1 hour. The resulting mixture was concentrated under reduced pressure and the residue purified using an Isco Combiflash system eluting with 0→5% MeOH in DCM as eluent to afford the title compound, 337.5 mg (96.6% yield). 1H NMR (CDCl3, 400 MHz): δ=1.33 (t, J=6.95 Hz, 3 H), 1.45 (d, J=13.64 Hz, 3 H), 3.22 (s, 1 H), 3.24 (s, 3 H), 3.26 (s, 1 H), 4.03-4.15 (m, 2 H), 4.34 (s, 2 H), 7.36-7.41 (m, 2 H), 7.50 (d, J=8.08 Hz, 4 H), 7.54 (d, J=8.84 Hz, 1 H), 8.20 (s, 1 H), 8.30 (d, J=9.35 Hz, 1 H). MS (ES+): m/z 600.0844 [MH+] (TOF, polar).
후처리
- customthe reaction mixture irradiated in a microwave reactor at 105° C. for 1 hour
- concentrationThe resulting mixture was concentrated under reduced pressure
- customthe residue purified
- washeluting with 0→5% MeOH in DCM as eluent
출처 및 근거
- ORD 기록
- ord-d1ca7fb349f24c50a0da553ea8738f0b
- 출처 데이터셋
- uspto-grants-2015_08
- 특허 번호
- US09096624B2
연결된 노트
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