Dimethylformamide → 4-Methyl-3-(9H-pyrido[2,3-b]indol-7-yl)-N-[3-(trifloromethyl)phenyl]benzamide trifluoro-acetate salt

HRID 1894899Notes

Reaction equation

HRID 1894899 reaction equation
Br[C:2]1[C:3]([NH:8][C:9]2[CH:10]=[C:11]([C:15]3[C:20]([CH3:21])=[CH:19][CH:18]=[C:17]([C:22]([NH:24][C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=4)=[O:23])[CH:16]=3)[CH:12]=[CH:13][CH:14]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.C([O-])(=[O:37])C.[Na+].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.CN([CH:65]=[O:66])C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:32][C:31]([F:34])([F:33])[C:65]([OH:66])=[O:37].[CH3:21][C:20]1[CH:19]=[CH:18][C:17]([C:22]([NH:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:32])([F:34])[F:33])[CH:26]=2)=[O:23])=[CH:16][C:15]=1[C:11]1[CH:10]=[C:9]2[C:14]([C:2]3[CH:7]=[CH:6][CH:5]=[N:4][C:3]=3[NH:8]2)=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 80271Tri-o-tolylphosphineHCID 517045Sodium AcetateHCID 692684343'-[(3-Bromopyridin-2-yl)amino]-6-methyl-N-[3-(trifluoromethyl)phenyl]biphenyl-3-carboxamide

Product 1

HCID 866219634-Methyl-3-(9H-pyrido[2,3-b]indol-7-yl)-N-[3-(trifloromethyl)phenyl]benzamide trifluoro-acetate saltYield 55%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

To a degassed mixture of 3′-[(3-bromopyridin-2-yl)amino]-6-methyl-N-[3-(trifluoromethyl)-phenyl]biphenyl-3-carboxamide (0.085 g, 0.16 mmol) and sodium acetate (20 mg, 0.24 mmol) in DMF (4 mL) was added tri-o-tolylphosphine (9.8 mg, 0.032 mmol) and palladium acetate (3.6 mg, 0.016 mmol). The mixture was degassed again and then was heated to vigorous reflux for 3 hours. The mixture was then cooled, filtered and purified by preparative HPLC-MS (C18 eluting with a gradient of MeCN/H2O containing 0.1% TFA), then lyophilized to afford the product (50 mg, 55%). 1H NMR (400 MHz, d6-DMSO): 12.03 (s, 1H), 10.54 (s, 1H), 8.62 (d, 1H), 8.46 (dd, 1H), 8.28 (d, 1H), 8.25 (s, 1H), 8.08 (d, 1H), 8.01-7.98 (m, 1H), 7.95 (dd, 1H), 7.59 (t, 1H), 7.55-7.49 (m, 2H), 7.45 (d, 1H), 7.33-7.26 (m, 2H), 2.35 (s, 3H); MS (ES) (M+H)=446.1.

Workup

  1. customThe mixture was degassed again
  2. temperaturewas heated
  3. temperatureto vigorous reflux for 3 hours
  4. temperatureThe mixture was then cooled
  5. filtrationfiltered
  6. custompurified by preparative HPLC-MS (C18
  7. washeluting with a gradient of MeCN/H2O containing 0.1% TFA),

Sources & evidence

ORD record
ord-44786799935a43da87c522f3e533d10c
Source dataset
uspto-grants-2013_08
Patent number
US08513270B2

Reaction notes

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