Hydroxyamine hydrochloride → N-(4-fluoro-3-methoxybenzyl)-6-((hydroxyimino)methyl)-2-methylpyrimidine-4-carboxamide

HRID 572641Notes

Reaction equation

[F:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:15]=[C:14]([CH:16]=O)[N:13]=[C:12]([CH3:18])[N:11]=2)=[O:9])=[CH:4][C:3]=1[O:21][CH3:22].[NH2:23][OH:24].Cl.C([O-])(=O)C.[Na+]>CCO>[F:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:15]=[C:14]([CH:16]=[N:23][OH:24])[N:13]=[C:12]([CH3:18])[N:11]=2)=[O:9])=[CH:4][C:3]=1[O:21][CH3:22]

Participants

Conditions

Temperature: 100 °C

Procedure

To a stirred solution of N-(4-fluoro-3-methoxybenzyl)-6-formyl-2-methylpyrimidine-4-carboxamide (6.75 g, 22.28 mmol, Preparation #8) and NH2OH.HCl (3.09 g, 44.56 mmol, Sisco Research Labs) in aqueous EtOH (75%, 100 mL), was added sodium acetate (5.48 g, 66.84 mmol, Spectrochem). The reaction mixture was heated to reflux at about 100° C. for about 1 h. Then reaction mixture was cooled to RT and poured into ice cold water (140 mL). The resulting solids were filtered, washed with hexane (100 mL) and dried under vacuum to afford N-(4-fluoro-3-methoxybenzyl)-6-((hydroxyimino)methyl)-2-methylpyrimidine-4-carboxamide as a light yellow solid 5.60 g (80%), 1H NMR (400 MHz, DMSO): δ 12.40 (s, 1H), 9.463-9.432 (t, J=8.1 Hz, 1H), 8.10 (s, 1H), 8.08 (s, 1H), 7.17-7.11 (m, 1H), 6.89-6.86 (m, 1H), 4.477-4.461 (d, J=6.4 Hz, 2H), 3.81 (s, 3H), 2.72 (s, 3H), MS m/z: 318.8 (M+H)+.

Workup

temperatureThe reaction mixture was heated
customThen reaction mixture
temperaturewas cooled to RT
filtrationThe resulting solids were filtered
washwashed with hexane (100 mL)
customdried under vacuum

Sources & evidence

ORD record: ord-fa2bf2b305874109851c536f28fee560
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09029409B2

Reaction notes

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