Acetonitrile--water (1/1) → 4-Cyano-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[3-(trifluoromethyl)phenyl]-benzamide

HRID 1894889Notes

Reaction equation

HRID 1894889 reaction equation
Cl[C:2]1[CH:20]=[CH:19][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)=[O:7])=[CH:4][C:3]=1[C:21]1[CH:29]=[C:28]2[C:24]([C:25]3[CH:33]=[N:32][CH:31]=[N:30][C:26]=3[NH:27]2)=[CH:23][CH:22]=1.C[C:35]#[N:36].O>CN(C=O)C.[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:35]([C:2]1[CH:20]=[CH:19][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)=[O:7])=[CH:4][C:3]=1[C:21]1[CH:29]=[C:28]2[C:24]([C:25]3[CH:33]=[N:32][CH:31]=[N:30][C:26]=3[NH:27]2)=[CH:23][CH:22]=1)#[N:36]

Participants

6

Reactant 2

HCID 18373917Acetonitrile--water (1/1)HCID 251526464-Chloro-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[3-(trifluoromethyl)phenyl]benzamide

Product 1

HCID 251526474-Cyano-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[3-(trifluoromethyl)phenyl]-benzamide

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
175 °C

Procedure

4-Chloro-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[3-(trifluoromethyl)phenyl]benzamide (60 mg TFA salt, 0.103 mmol), zinc cyanide (121 mg, 1.03 mmol), and tetrakis(triphenylphosphine)-palladium(0) (59 mg, 0.051 mmol) were stirred in DMF (3 mL) and the mixture was flushed with nitrogen. The mixture was heated in a microwave reactor at 175° C. for 1 h. LCMS showed 65% conversion to the desired product, M+H 458. The product was isolated by prep LCMS using a 30 mm×100 mm C18 column; 35% CH3CN—H2O (0.1% TFA), 1 min, to 55% at 6 min; 60 mL/min; detector set at m/z 458. The HPLC fractions were rotovaped to give 23 mg of the produce as a TFA salt. The product was purified by prep HPLC using a 19 mm×100 mm C18 column; 50% CH3CN—H2O (0.1% AcOH), 1 min, to 75% at 6 min; 30 mL/min; detector set at 254 nm; retention time, 3.9 min. Fractions containing pure product were combined and freeze-dried. yield 4 mg. 1H NMR (DMSO-d6) δ 12.88 (s, 1H, NH); 10.83 (s, 1H, amide NH); 9.61 (s, 1H, NH); 9.07 (s, 1H); 8.48 (d, 1H); 8.29 (d, 1H); 8.23 (s, 1H); 8.20 (d, 1H); 8.14 (dd, 1H); 8.06 (d, 1H); 7.89 (d, 1H); 7.68 (dd, 1H); 7.62 (t, 1H); 7.49 (d, 1H).

Workup

  1. customthe mixture was flushed with nitrogen
  2. customThe product was isolated by prep LCMS
  3. customto give 23 mg of the

Sources & evidence

ORD record
ord-e4e70d326dcc41b895a34cd9beeb7305
Source dataset
uspto-grants-2013_08
Patent number
US08513270B2

Reaction notes

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