Dimethylformamide → HCID 67367542, compound

HRID 1910918Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[O:10])[N:8]3[CH2:11][CH2:12][NH:13][C:7]3([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[CH2:6][N:5]2[CH:22]=1.[CH3:23][N:24](C=O)C>[C-]#N.[Zn+2].[C-]#N>[CH3:21][O:20][C:17]1[CH:18]=[CH:19][C:14]([C:7]23[NH:13][CH2:12][CH2:11][N:8]2[C:9](=[O:10])[C:4]2[N:5]([CH:22]=[C:2]([C:23]#[N:24])[CH:3]=2)[CH2:6]3)=[CH:15][CH:16]=1

Participants

Conditions

Temperature: 160 °C

Procedure

7-bromo-10a-(4-methoxyphenyl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (100 mg, 0.28 mmol), zinc cyanide (50 mg, 0.42 mmol) and palladium(0) tetrakistriphenylphosphine (32 mg, 0.03 mmol) were suspended in dry DMF (3 mL) in a microwave vial flushed with argon. The mixture was heated in the microwave reactor at 160° C. for 20 minutes. A saturated aqueous solution of NaHCO3 (50 mL) was added and the mixture extracted with CH2Cl2 containing 20% of isopropyl alcohol. The organic layers were dried (MgSO4), filtrated and concentrated in vacuo. The resulting residue was purified by flash chromatography (Biotage SP4, 12 g cartridge, gradient 0-5% methanol in CH2Cl2) to give 10a-(4-methoxyphenyl)-5-oxo-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazine-7-carbonitrile (50 mg, yield 58%) ESI-MI m/z [M+H]+ 308.9. Used in the next step without further purification.

Workup

customvial flushed with argon
additionA saturated aqueous solution of NaHCO3 (50 mL) was added
extractionthe mixture extracted with CH2Cl2 containing 20% of isopropyl alcohol
dry with materialThe organic layers were dried (MgSO4)
filtrationfiltrated
concentrationconcentrated in vacuo
customThe resulting residue was purified by flash chromatography (Biotage SP4, 12 g cartridge, gradient 0-5% methanol in CH2Cl2)

Sources & evidence

ORD record: ord-63306da58b0948808039d6792dda809c
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08604034B2

Reaction notes

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