HCID 57456316, compound → HCID 59852752, compound

HRID 2373930Notes

Reaction equation

[CH2:1]([O:8][C:9]1[C:10]([F:29])=[C:11]([C:15]2[N:16]=[C:17]([CH:25]3[CH2:28][CH2:27][CH2:26]3)[N:18]3[CH:23]=[CH:22][N:21]=[C:20](Cl)[C:19]=23)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC1C(F)=C(C(NC(C2CCC2)=O)C2C(Cl)=NC=C[N:46]=2)C=CC=1)C1C=CC=CC=1>O=P(Cl)(Cl)Cl>[NH2:46][C:20]1[C:19]2[N:18]([C:17]([CH:25]3[CH2:28][CH2:27][CH2:26]3)=[N:16][C:15]=2[C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:10]=2[F:29])[CH:23]=[CH:22][N:21]=1

Participants

Conditions

Temperature: 55 °C

Procedure

1-(3-Benzyloxy-2-fluorophenyl)-8-chloro-3-cyclobutylimidazo[1,5-a]pyrazine: Cyclobutanecarboxylic acid [(3-benzyloxy-2-fluoro-phenyl)-(3-chloro-pyrazin-2-yl)-methyl]-amide (0.850 g, 2 mmole) was dissolved in POCl3 (6 mL) and heated at 55° C. overnight. The excess POCl3 was removed in vacuo. The residue was cooled to 0° C. and charged with a saturated solution of NH3 in 2-propanol (6 mL). The mixture was left overnight at room temperature. The separated solid was then filtered and washed with methylene chloride. The filtrate was evaporated to dryness and purified by silica-gel column chromatography using hexane:ethyl acetate (60:40) as the eluant to afford the title compound (615 mg, 75%). FAB-MS: m/z 408.3 (M+H)+.

Workup

customThe excess POCl3 was removed in vacuo
temperatureThe residue was cooled to 0° C.
additioncharged with a saturated solution of NH3 in 2-propanol (6 mL)
filtrationThe separated solid was then filtered
washwashed with methylene chloride
customThe filtrate was evaporated to dryness
custompurified by silica-gel column chromatography

Sources & evidence

ORD record: ord-aad5b28a0cfd419da1442e9ac139e5d9
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07459554B2

Reaction notes

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