Dimethylformamide → 1-(3-Benzyloxy-phenyl)-8-chloro-3-methylsulfanyl-imidazo[1,5-a]pyrazine

HRID 1992427Notes

Reaction equation

[CH3:1][S:2][C:3](=O)[NH:4][CH:5]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:14]=1)[C:6]1[C:11]([Cl:12])=[N:10][CH:9]=[CH:8][N:7]=1.CN(C=O)C.O=P(Cl)(Cl)Cl>CC#N>[CH2:20]([O:19][C:15]1[CH:14]=[C:13]([C:5]2[N:4]=[C:3]([S:2][CH3:1])[N:7]3[CH:8]=[CH:9][N:10]=[C:11]([Cl:12])[C:6]=23)[CH:18]=[CH:17][CH:16]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of [(3-benzyloxy-phenyl)-(3-chloro-pyrazin-2-yl)-methyl]-thiocarbamic acid S-methyl ester (200 mg, 0.0005 mol) in MeCN (10 mL) and DMF (0.12 mL, 0.0015 mol) was added POCl3 (0.14 mL, 0.0015 mol); the resulting mixture was stirred at 55° C. overnight. The mixture was quenched with 2N NH3/iPrOH, then diluted with EtOAc, washed with brine and dried over anhydrous sodium sulfate. The residue was purified by silica gel chromatography (Hex.: EtOAc=80:20→70:30) to give a yellow solid. 1H-NMR (CDCl3) confirmed a mixture of the desired product and starting material in ca. 1:1 ratio, which was taken on to next step.

Workup

customThe mixture was quenched with 2N NH3/iPrOH
additiondiluted with EtOAc
washwashed with brine
dry with materialdried over anhydrous sodium sulfate
customThe residue was purified by silica gel chromatography (Hex.: EtOAc=80:20→70:30)
customto give a yellow solid

Sources & evidence

ORD record: ord-13c2a1593384416fbea174c5602fa00d
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07648987B2

Reaction notes

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