Dimethylformamide → 2-Chloro-5-(pivalamidomethyl)-N-(8-((3-(trifluoromethyl)phenyl)amino)quinolin-4-yl)benzamide

HRID 1469814Notes

Reaction equation

HRID 1469814 reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]1[CH:4]=[C:5]([NH:9][C:10]2[C:19]3[C:14](=[C:15]([NH2:20])[CH:16]=[CH:17][CH:18]=3)N=CC=2)[CH:6]=[CH:7][CH:8]=1.[H-].[Na+].[Cl:25][C:26]1[CH:43]=[CH:42][C:41]([CH2:44][NH:45][C:46](=[O:51])[C:47]([CH3:50])([CH3:49])[CH3:48])=[CH:40][C:27]=1[C:28]([O:30]C1C=CC([N+]([O-])=O)=CC=1)=O.C[N:53]([CH:55]=O)[CH3:54]>>[Cl:25][C:26]1[CH:43]=[CH:42][C:41]([CH2:44][NH:45][C:46](=[O:51])[C:47]([CH3:48])([CH3:49])[CH3:50])=[CH:40][C:27]=1[C:28]([NH:20][C:15]1[C:16]2[C:54](=[C:10]([NH:9][C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:21])[F:22])[CH:4]=3)[CH:19]=[CH:18][CH:17]=2)[N:53]=[CH:55][CH:14]=1)=[O:30]

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 866922384-Nitrophenyl 2-chloro-5-(pivalamidomethyl)benzoateHCID 86692281N-(3-(trifluoromethyl)phenyl)quinoline-4,8-diamine

Product 1

HCID 866922802-Chloro-5-(pivalamidomethyl)-N-(8-((3-(trifluoromethyl)phenyl)amino)quinolin-4-yl)benzamide

Conditions

Temperature
2.5 °C

Procedure

To a solution of N-(3-(trifluoromethyl)phenyl)quinoline-4,8-diamine (Intermediate-12, 80 mg, 0.264 mmol) in DMF (2 mL) was added NaH (26 mg, 0.65 mmol, 60% in mineral oil) at 0° C. and the reaction mixture was stirred at 0-5° C. for 30 minutes. Then a solution of 4-nitrophenyl 2-chloro-5-(pivalamidomethyl)benzoate (Intermediate-13, 123 mg, 0.314 mmol) in DMF (1 mL) was added to the reaction mixture at 0° C. and the reaction mixture was stirred at 0° C.—rt for 2 h. Then the reaction mixture was quenched with water and was extracted with EtOAc. The organic layer was washed with brine, separated, dried, filtered and concentrated. The residue was purified by column chromatography to afford 15 mg of the title product. 1H NMR (300 MHz, DMSO-d6): δ 10.92 (s, 1H), 9.07 (s, 1H), 8.86 (d, J=4.8 Hz, 1H), 8.21-8.18 (m, 2H), 7.80-7.57 (m, 3H), 7.59-7.54 (m, 5H), 7.39 (d, J=8.4 Hz, 1H), 7.25 (d, J=7.2 Hz, 1H), 4.32 (d, J=6.0 Hz, 2H), 1.19 (s, 9H); MS [M+H]+: 555.25.

Workup

  1. stirringthe reaction mixture was stirred at 0° C.—rt for 2 h
  2. customThen the reaction mixture was quenched with water
  3. extractionwas extracted with EtOAc
  4. washThe organic layer was washed with brine
  5. customseparated
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-6bafbb161c4f4c8f91ccf29b45c45746
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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