Dimethylformamide → 3-[5-(4-Aminothieno[2,3-d]pyrimidin-6-yl)-1-methyl-1H-imidazol-4-yl]benzonitrile

HRID 32632Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[CH:10][N:11]([CH3:23])[C:12]=2[C:13]2[S:22][C:16]3[N:17]=[CH:18][N:19]=[C:20]([NH2:21])[C:15]=3[CH:14]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:24][N:25](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:21][C:20]1[C:15]2[CH:14]=[C:13]([C:12]3[N:11]([CH3:23])[CH:10]=[N:9][C:8]=3[C:4]3[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=3)[C:24]#[N:25])[S:22][C:16]=2[N:17]=[CH:18][N:19]=1

Participants

Conditions

Temperature: 80 °C

Procedure

6-[4-(3-Bromophenyl)-1-methyl-1H-imidazol-5-yl]thieno[2,3-d]pyrimidin-4-amine (Example 50) (192 mg) was stirred with zinc cyanide (118 mg) and tetrakis(triphenylphosphine)palladium (116 mg) in DMF (7 mL), degassed, then heated under an inert atmosphere at 80° C. for 20 hours. The solvent was evaporated and the residue was purified by flash chromatography on silica using 0-100% EtOAc in DCM then 0-20% MeOH in DCM as eluent. Further purification by preparative RPBPLC using an MeCN/water/formic acid gradient gave the title compound as a solid (28 mg, 16%);

Workup

customdegassed
customThe solvent was evaporated
customthe residue was purified by flash chromatography on silica using 0-100% EtOAc in DCM
customFurther purification by preparative RPBPLC

Sources & evidence

ORD record: ord-1c0feb97983e42f0819bc2d7cfbe1541
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07427616B2

Reaction notes

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