2-Fluoro-5-(trifluoromethyl)phenyl isocyanate → n-{4-[4-Amino-7-(4-pyridinyl)thieno[3,2-c]pyridin-3-yl]phenyl}-n'-[2-fluoro-5-(trifluoromethyl)phenyl]urea

HRID 17133노트

반응식

HRID 17133 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[C:13]([NH2:23])=[N:14][CH:15]=[C:16]([C:17]4[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=4)[C:11]=3[S:10][CH:9]=2)=[CH:4][CH:3]=1.[F:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][C:26]=1[N:35]=[C:36]=[O:37]>CN(C=O)C.C1COCC1.O>[NH2:23][C:13]1[C:12]2[C:8]([C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:36]([NH:35][C:26]4[CH:27]=[C:28]([C:31]([F:32])([F:34])[F:33])[CH:29]=[CH:30][C:25]=4[F:24])=[O:37])=[CH:7][CH:6]=3)=[CH:9][S:10][C:11]=2[C:16]([C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)=[CH:15][N:14]=1

참가 물질

6

반응물 2

HCID 27333802-Fluoro-5-(trifluoromethyl)phenyl isocyanateHCID 184507433-(4-Aminophenyl)-7-(pyridin-4-yl)thieno[3,2-c]pyridin-4-amine

생성물 1

HCID 11156716n-{4-[4-Amino-7-(4-pyridinyl)thieno[3,2-c]pyridin-3-yl]phenyl}-n'-[2-fluoro-5-(trifluoromethyl)phenyl]urea수율 46.2%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

실험 절차

A −20° C. solution of Example 121B (0.18 g, 0.57 mmol) in DMF (3 mL) and THF (3 mL) was treated dropwise with 1-fluoro-2-isocyanato-4-(trifluoromethyl)benzene (0.085 mL, 0.57 mmol) and warmed to room temperature over 1.5 hours. The resulting mixture was diluted with water and extracted twice with ethyl acetate. The combined extracts were dried (Na2SO4), filtered, concentrated and the residue was purified by flash column chromatography on silica gel with 3-5% methanol/dichloromethane to provide 138 mg of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 5.74 (s, 2H), 7.44 (d, J=8.48 Hz, 3H), 7.51 (d, J=10.85 Hz, 1H), 7.55 (s, 1H), 7.64 (d, J=8.82 Hz, 2H), 7.71-7.72 (m, 1H), 7.74 (d, J=1.70 Hz, 1H), 8.10 (s, 1H), 8.64 (dd, J=7.29, 2.20 Hz, 1H), 8.67-8.69 (m, 1H), 8.70 (d, J=1.70 Hz, 1H), 8.98 (d, J=2.71 Hz, 1H), 9.40 (s, 1H); MS (ESI(+)) m/e 524 (M+H)+.

후처리

  1. extractionextracted twice with ethyl acetate
  2. dry with materialThe combined extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customthe residue was purified by flash column chromatography on silica gel with 3-5% methanol/dichloromethane

출처 및 근거

ORD 기록
ord-2007dab67afc443baba3f58d9a04d804
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07737160B2

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