Dimethylformamide → HCID 16042015, compound

HRID 252194Notes

Reaction equation

HRID 252194 reaction equation
[NH2:1][C:2]1[C:11]([C:12]2[C:13]([Cl:32])=[C:14]([NH:19][C:20](=[O:31])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[CH:15]=[CH:16][C:17]=2[Cl:18])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=CC=2)[N:3]=1.[H-].[Na+].[C:35]([N:39]=[C:40]=[O:41])([CH3:38])([CH3:37])[CH3:36].[CH3:42][N:43](C=O)C>CCOC(C)=O>[C:35]([NH:39][C:40](=[O:41])[NH:1][C:2]1[C:11]([C:12]2[C:13]([Cl:32])=[C:14]([NH:19][C:20](=[O:31])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:30])[F:29])[CH:22]=3)[CH:15]=[CH:16][C:17]=2[Cl:18])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[N:43][CH:42]=2)[N:3]=1)([CH3:38])([CH3:37])[CH3:36]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 62412tert-Butyl isocyanateHCID 66846503HCID 66846503, compound

Product 1

HCID 16042015HCID 16042015, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-[3-(2-amino-quinolin-3-yl)-2,4-dichloro-phenyl]-3-trifluoromethyl-benzamide (100.0 mg, 0.210 mmol) in DMF (4.0 mL) is added NaH (60%, 10.9 mg, 0.273 mmol) at room temperature. After the mixture is stirred for 30 minutes at room temperature, tert-butyl isocyanate (24.9 mg, 0.252 mmol) is added and the mixture is stirred 6 hours. The reaction mixture is diluted with EtOAc and washed with saturated K2CO3, brine and water. The organic layer is dried, filtered and concentrated to give crude product, which is purified by flash silica gel column eluting with CH2Cl2 (100%) gradient to CH2Cl2/MeOH(NH3, 2N) (95/5) to give the final product as a solid: 1H NMR 400 MHz (CDCl3) δ 9.97 (s, 1H), 9.56 (s, 1H), 8.80 (m, 2H), 8.44 (s, 1H), 8.26 (s, 1H), 8.24 (s, 1H), 8.12 (d, 1H), 7.94 (m, 2H), 7.37 (t, 1H), 7.67 (d, 1H); MS m/z 577.70 (M+1).

Workup

  1. stirringthe mixture is stirred 6 hours
  2. washwashed with saturated K2CO3, brine and water
  3. customThe organic layer is dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give crude product, which
  7. customis purified by flash silica gel column
  8. washeluting with CH2Cl2 (100%) gradient to CH2Cl2/MeOH(NH3, 2N) (95/5)

Sources & evidence

ORD record
ord-f33deb56dc484413b111768cc81e3ecd
Source dataset
uspto-grants-2011_01
Patent number
US07868018B2

Reaction notes

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