Dimethylformamide → HCID 178482681, compound

HRID 416787Notes

Reaction equation

Br[C:2]1[C:3]([N:20]2[CH2:25][CH2:24][N:23]([CH2:26][C:27]([NH:29][C:30]3[S:31][CH:32]=[CH:33][N:34]=3)=[O:28])[CH2:22][CH2:21]2)=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([N:17]([CH3:19])[CH3:18])=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1.[CH3:35][N:36](C=O)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[C-]#N.[C-]#N.[Zn+2]>[C:35]([C:2]1[C:3]([N:20]2[CH2:25][CH2:24][N:23]([CH2:26][C:27]([NH:29][C:30]3[S:31][CH:32]=[CH:33][N:34]=3)=[O:28])[CH2:22][CH2:21]2)=[C:4]2[N:10]=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([N:17]([CH3:19])[CH3:18])=[CH:15][CH:16]=3)[NH:8][C:5]2=[N:6][CH:7]=1)#[N:36]

Participants

Conditions

Temperature: 180 °C

Procedure

A solution of 2-(4-(6-bromo-2-(4-(dimethylamino)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamide (75 mg, 0.14 mmol) in degassed DMF (1 mL) containing Pd2 dba3 (0.05 eq, 0.0069 mmol, 6 mg), dppf (0.1 eq, 0.014 mmol, 8 mg) and Zn(CN)2 (1.5 eq, 0.21 mmol, 24 mg) was stirred with microwave heating at 180° C. for 30 minutes. After this time, further Pd2(dba)3 (6 mg), dppf (8 mg) and Zn(CN)2 (24 mg) were added and the mixture stirred under the same conditions for a further 30 minutes. hplc then showed partial conversion to the desired compound. Concentration in vacuo and purification of a small sample by semi-preparative hplc gave the pure product as a colourless solid; 1H-NMR (500 MHz, DMSO-d6) 2.80 (t, br, J=4.7 Hz, 4H, piperazine N(CH2)2), 3.00 (s, 6H, N(CH3)2), 3.42 (s, 2H, NCH2CO), 4.11 (s, br, 4H, piperazine N(CH2)2), 6.82 (d, J=9.0 Hz, 2H, N,N-dimethylaminophenyl), 7.24 (d, J=3.5 Hz, 1H, thiazole H-4 or H-5), 7.50 (d, J=3.5 Hz, 1H, thiazole H-4 or H-5), 7.99 (d, J=9.0 Hz, 2H, N,N-dimethylaminophenyl), 8.23 (s, 1H, imidazo[4,5-b]pyridine H-5), 11.91 (br s, 1H, CONH), 13.46 (br s, 1H, imidazo[4,5-b]pyridine NH);

Workup

stirringthe mixture stirred under the same conditions for a further 30 minutes

Sources & evidence

ORD record: ord-f975a2f1839d41f8a49e6a028fd47606
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088761B2

Reaction notes

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