Tri-o-tolylphosphine → 4-Chloro-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[3-(trifluoromethyl)phenyl]benzamide

HRID 77716Notes

Reaction equation

HRID 77716 reaction equation
C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C([O-])(=O)C.[Na+].[Cl:28][C:29]1[C:34]([C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([NH:41][C:42]3[C:47](I)=[CH:46][N:45]=[CH:44][N:43]=3)[CH:36]=2)=[CH:33][C:32]([C:49]([NH:51][C:52]2[CH:57]=[CH:56][CH:55]=[C:54]([C:58]([F:61])([F:60])[F:59])[CH:53]=2)=[O:50])=[CH:31][CH:30]=1>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:28][C:29]1[CH:30]=[CH:31][C:32]([C:49]([NH:51][C:52]2[CH:57]=[CH:56][CH:55]=[C:54]([C:58]([F:61])([F:60])[F:59])[CH:53]=2)=[O:50])=[CH:33][C:34]=1[C:35]1[CH:36]=[C:37]2[C:38]([C:47]3[CH:46]=[N:45][CH:44]=[N:43][C:42]=3[NH:41]2)=[CH:39][CH:40]=1

Participants

6

Reactant 3

HCID 80271Tri-o-tolylphosphineHCID 517045Sodium AcetateHCID 69047842HCID 69047842, compound

Product 1

HCID 251526464-Chloro-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[3-(trifluoromethyl)phenyl]benzamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

tri-o-Tolylphosphine (2.0E1 mg, 0.064 mmol) was stirred in DMF (2 mL). The mixture was degassed by bubbling nitrogen through it until all additions were complete. To the mixture was added palladium acetate (7.2 mg, 0.032 mmol), and the resulting mixture was stirred at 20° C. for 5 min. To the resulting mixture was added sodium acetate (39.5 mg, 0.482 mmol) and 6-chloro-3′-[(5-iodopyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]biphenyl-3-carboxamide (0.191 g, 0.321 mmol). The resulting mixture was heated to reflux. After 4 h, LCMS showed complete reaction to give the desired product, M+H 467; and small amounts of reduction product (M+H 469) and de-chlorination product (M+H 433). The product was isolated by prep HPLC using a 30 mm×100 mm C18 column; 35% CH3CN—H2O (0.1% TFA), 1.5 min, to 55% at 6 min; 60 mL/min; detector set at 285 nm; retention time, 4.9 min; retention time of the de-chlorination product, 4.5 min. The HPLC fractions were freeze-dried to yield product TFA salt, a white solid; 1H NMR (DMSO-d6) δ 13.0 (s, 1H, NH); 10.7 (s, 1H, amide NH); 9.63 (s, 1H, NH); 9.11 (s, 1H); 8.44 (d, 1H); 8.36 (s, 1H); 8.27 (s, 1H); 8.09 (d, 1H); 8.02 (t, 2H); 7.95 (s, 1H); 7.84 (d, 1H); 7.70 (t, 1H); 7.62 (t, 1H); 7.47 (d, 1H).

Workup

  1. customThe mixture was degassed
  2. customby bubbling nitrogen through it until all additions
  3. temperatureThe resulting mixture was heated to reflux
  4. waitAfter 4 h
  5. customreaction

Sources & evidence

ORD record
ord-9a5b3c67dbed4696a1e2c3848b62833c
Source dataset
uspto-grants-2014_09
Patent number
US08841318B2

Reaction notes

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