Hydrochloric Acid → HCID 178517769, compound

HRID 1880203Notes

Reaction equation

[CH2:1]([N:8](C)[C:9]1[C:14]([F:15])=[CH:13][N:12]=[C:11](Cl)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-:18].[K+].Cl.O1CCOC[CH2:22]1.O>O>[CH2:2]([CH2:1][NH:8][C:9]1[C:14]([F:15])=[CH:13][N:12]=[C:11]([OH:18])[N:10]=1)[C:7]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:22]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a suspension of N-benzyl-2-chloro-5-fluoro-N-methylpyrimidin-4-amine (0.075 g, 0.30 mmol) in dioxane/H2O (1:1, 2 mL total volume) was added potassium hydroxide (KOH; 0.17 g, 3.0 mmol). The mixture was warmed to 100° C. and stirred for 72 h. The reaction mixture was diluted with H2O (5 mL), and the pH was adjusted to 7 with 2 N HCl. The resulting white precipitate was collected by vacuum filtration, but the majority of the product remained in the aqueous phase. The solid and filtrate were combined and the solvent was removed by azeotropic distillation with CH3CN in vacuo. The residue was dissolved/suspended in CH2Cl2 (25 mL), adsorbed onto Celite (3.0 g) and purified by normal phase chromatography (24 g SiO2; gradient, MeOH/CH2Cl2) to give 4-(benzylmethylamino)-5-fluoropyrimidin-2-ol (0.016 g, 23%) as a white solid: mp 122.8-123.6° C.; 1H NMR (300 MHz, CDCl3) δ 12.72 (s, 1H), 7.42-7.14 (m, 6H), 4.88 (s, 2H), 3.20 (d, J=3.2, 3H); ESIMS m/z 235 (M+2)+, 232 (M−H)−.

Workup

filtrationThe resulting white precipitate was collected by vacuum filtration
customthe solvent was removed by azeotropic distillation with CH3CN in vacuo
custompurified by normal phase chromatography (24 g SiO2; gradient, MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-14862dfcd183412790a1fe09ea692726
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08318758B2

Reaction notes

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