Dimethylformamide → 4-Methyl-3-(9H-pyrimido[4,5-b]indol-6-yl)-N-[3-(trifluoromethyl)phenyl]benzamide

HRID 77713Notes

Reaction equation

HRID 77713 reaction equation
I[C:2]1[C:3]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([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:11][CH:10]=2)=[N:4][CH:5]=[N:6][CH:7]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C([O-])(=O)C.[Na+].CN(C=O)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[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:33])([F:32])[F:34])[CH:26]=2)=[O:23])=[CH:16][C:15]=1[C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:3]1[N:4]=[CH:5][N:6]=[CH:7][C:2]2=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 80271Tri-o-tolylphosphineHCID 517045Sodium AcetateHCID 690435614'-[(5-Iodopyrimidin-4-yl)amino]-6-methyl-N-[3-(trifluoromethyl)phenyl]biphenyl-3-carboxamide

Product 1

HCID 251526454-Methyl-3-(9H-pyrimido[4,5-b]indol-6-yl)-N-[3-(trifluoromethyl)phenyl]benzamideYield 57.5%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

4′-[(5-Iodopyrimidin-4-yl)amino]-6-methyl-N-[3-(trifluoromethyl)phenyl]biphenyl-3-carboxamide (0.168 g, 0.000292 mol) was mixed with palladium acetate (0.013 g, 0.000058 mol), tri-o-tolylphosphine (0.036 g, 0.00012 mol) and sodium acetate (0.036 g, 0.00044 mol) in DMF (2.0 mL, 0.026 mol) and the mixture was heated to reflux for 4 hours. Mass spectral analysis showed ˜60% conversion. The reaction was continued for 2.5 hours at which time LCMS analysis showed ˜75% conversion. The reaction was extracted with ethyl acetate and the organic extracts were washed with water, saturated NaCl, dried (MgSO4) and concentrated in vacuo. The concentrate was chromatographed on silica gel using 2:1 EtOAc/hexanes to give the product (75 mg, 57% yield). 1H NMR (CDCl3): δ □ 9.23 (s, 1H), 9.10 (brs, 1H), 9.06 (s, 1H), 8.08 (s, 1H), 7.80-8.00 (m, 5H), 7.39-7.84 (m, 5H), 2.39 (s, 3H). MS (EI) m/z=447 (M+H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 4 hours
  3. extractionThe reaction was extracted with ethyl acetate
  4. washthe organic extracts were washed with water, saturated NaCl
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe concentrate was chromatographed on silica gel using 2:1 EtOAc/hexanes

Sources & evidence

ORD record
ord-50de7210cfb14566893d88dd39ec52be
Source dataset
uspto-grants-2014_09
Patent number
US08841318B2

Reaction notes

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