Pyridine → Isopropylamine

HRID 1619065Notes

Reaction equation

[F:1][C:2]1[C:3]([O:33][CH3:34])=[N:4][C:5]([N:9]2[CH2:17][C@@H:16]3[C@@:11]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)([N:12]=[C:13]([NH:18]C(=O)C4C=CC=CC=4)[S:14][CH2:15]3)[CH2:10]2)=[N:6][C:7]=1[CH3:8].N1C=CC=CC=1.[ClH:41].CON>C(O)C>[CH:7]([NH2:6])([CH3:8])[CH3:2].[ClH:41].[F:1][C:2]1[C:3]([O:33][CH3:34])=[N:4][C:5]([N:9]2[CH2:17][C@@H:16]3[C@@:11]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)([N:12]=[C:13]([NH2:18])[S:14][CH2:15]3)[CH2:10]2)=[N:6][C:7]=1[CH3:8]

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of N-[(4aR,7aS)-6-(5-fluoro-4-methoxy-6-methyl-pyrimidin-2-yl)-7a-phenyl-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (68 mg, 0.14 mmol) in ethanol (5.0 mL) is added pyridine (0.115 mL, 1.42 mmol) and O-methylhydroxylamine hydrochloride (118 mg, 1.42 mmol). The mixture is heated to 55° C. for 16 hours, cooled to ambient temperature, and concentrated to dryness. The residue is purified by silica gel flash chromatography, eluting with a gradient of 0 to 100% of hexane/ethyl acetate:10% isopropyl amine to give the free base form of the title compound as a colorless oil. Dissolve this residue in dichloromethane (3 mL) and add 4 N HCl in dioxane (2 mL) and stir for 5 minutes. The solution is then concentrated to give the title compound as an off white solid (50 mg, 86%). ES/MS (m/e) 374.0 (M+H).

Workup

temperaturecooled to ambient temperature
concentrationconcentrated to dryness
customThe residue is purified by silica gel flash chromatography
washeluting with a gradient of 0 to 100% of hexane/ethyl acetate

Sources & evidence

ORD record: ord-d79a6679a13442adb827ec07936c89cb
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772282B2

Reaction notes

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