Hydrochloric Acid → HCID 57504950, compound

HRID 2060807Notes

Reaction equation

[ClH:1].[F:2][C:3]1[CH:8]=[C:7]([F:9])[C:6]([C:10]2[CH:11]=[N:12][CH:13]=[C:14]([F:16])[CH:15]=2)=[CH:5][C:4]=1[C@:17]12[CH2:25][O:24][CH2:23][C@H:22]1[CH2:21][S:20][C:19]([NH:26]C(=O)C1C=CC=CC=1)=[N:18]2>CO>[ClH:1].[ClH:1].[F:2][C:3]1[CH:8]=[C:7]([F:9])[C:6]([C:10]2[CH:11]=[N:12][CH:13]=[C:14]([F:16])[CH:15]=2)=[CH:5][C:4]=1[C@:17]12[CH2:25][O:24][CH2:23][C@H:22]1[CH2:21][S:20][C:19]([NH2:26])=[N:18]2

Participants

Conditions

Temperature: 90 °C

Procedure

N Aqueous hydrochloric acid (8.70 mL) is added to N-((4aS,7aS)-7a-(2,4-difluoro-5-(5-fluoropyridin-3-yl)phenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (0.252 g, 0.435 mmol) in methanol (4 mL) and the mixture is heated to 90° C. After 18 hours, the heat is removed and the pH of the reaction mixture is adjusted to basic with 5 N aqueous sodium hydroxide. The mixture is extracted three times with 10% isopropyl alcohol in dichloromethane. The organic layer is concentrated under reduced pressure and the resulting residue is purified by radial chromatography eluting with 3% 2 M ammonia in methanol:dichloromethane to give the title compound as the freebase. The free base is dissolved in minimal dichloromethane and 1 M hydrogen chloride in ether is added in excess. Hexane (1 mL) is added and the solvent is removed under reduced pressure to give the title compound (0.129 g, 67%). ES/MS m/e: 366 (M+1).

Workup

customthe heat is removed
extractionThe mixture is extracted three times with 10% isopropyl alcohol in dichloromethane
concentrationThe organic layer is concentrated under reduced pressure
customthe resulting residue is purified by radial chromatography
washeluting with 3% 2 M ammonia in methanol

Sources & evidence

ORD record: ord-a6a707bfc0b44ffda22327500dca3bea
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278441B2

Reaction notes

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