Hydrochloric Acid → HCID 178517769, compound

HRID 1260417Notes

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 (7.5 g, 27.1 mmol) in dioxane/H2O (1:1, 186 mL total volume) was added potassium hydroxide (KOH; 1.7 g, 27.1 mmol). The mixture was warmed to 100° C. and stirred for 72 h. The reaction mixture was diluted with H2O (50 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 flash chromatography (24 g SiO2; gradient, MeOH/CH2Cl2) to give 4-(benzylmethylamino)-5-fluoropyrimidin-2-ol (4.4 g, 45%) 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 flash chromatography (24 g SiO2; gradient, MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-83303a1a65b1477b9f8b8603b2f9060b
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08470839B2

Reaction notes

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