Dimethylformamide → HCID 178509758, compound

HRID 655722Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:13]2[N:14]=[CH:15][NH:16][C:17](=[O:18])[C:12]=2[CH:11]=[N:10]1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:61][N:62](C=O)C>[C-]#N.[Zn+2].[C-]#N.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]>[Cl:8][C:4]1[C:3]([N:9]2[C:13]3=[N:14][CH:15]=[N:16][C:17]([OH:18])=[C:12]3[CH:11]=[N:10]2)=[C:2]([CH:7]=[CH:6][CH:5]=1)[C:61]#[N:62]

Participants

Conditions

Temperature: 160 °C

Procedure

1-(2-bromo-6-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (Intermediate AH4) (1012 mg, 3.11 mmol) and zinc cyanide (329 mg, 2.80 mmol) were dissolved in DMF (15 mL). Sealed into a microwave tube. The tube was purged with nitrogen. 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (180 mg, 0.31 mmol) and tris(dibenzylideneacetone)dipalladium(0) (142 mg, 0.16 mmol) added. The reaction was heated to 160° C. for 15 minutes in the microwave reactor, then allowed to cool to ambient temperature. The DMF was removed by evaporation. The crude product was absorbed onto silica and then purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM to afford the product (769 mg, 91%). 1H NMR (400 MHz, DMSO) δ 7.89-7.83 (1H, t), 8.14 (1H, s), 8.15 (2H, d), 8.49 (1H, s), 12.56 (1H, s); m/z (ES+) (M+H)+=272; HPLC tR=1.29 min.

Workup

customSealed into a microwave tube
customThe tube was purged with nitrogen
temperatureto cool to ambient temperature
customThe DMF was removed by evaporation
customThe crude product was absorbed onto silica
custompurified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM

Sources & evidence

ORD record: ord-dfeba82855c643d3bd766b41278000bd
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08071608B2

Reaction notes

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