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 17133Notes

Reaction equation

HRID 17133 reaction equation
[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

Participants

6

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-2007dab67afc443baba3f58d9a04d804
Source dataset
uspto-grants-2010_06
Patent number
US07737160B2

Reaction notes

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