Methanol → HCID 66855357, compound

HRID 252141Notes

Reaction equation

Cl[C:2]1[C:7]([F:8])=[CH:6][N:5]=[C:4]([N:9]2[CH2:13][CH2:12][C@H:11]([NH:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=3[Cl:23])[CH2:10]2)[N:3]=1.[CH3:24][O-:25].[Na+].CO>COCCOC>[Cl:23][C:17]1[CH:18]=[C:19]([Cl:22])[CH:20]=[CH:21][C:16]=1[CH2:15][NH:14][CH:11]1[CH2:12][CH2:13][N:9]([C:4]2[N:3]=[C:2]([O:25][CH3:24])[C:7]([F:8])=[CH:6][N:5]=2)[CH2:10]1

Participants

Conditions

Temperature: 70 °C

Procedure

Dissolve (S)-[1-(4-chloro-5-fluoropyrimidin-2-yl)-pyrrolidin-3-yl]-(2,4-dichlorobenzyl)-amine (318 mg, 0.84 mmol) in dry 1,2-dimethoxyethane (20 mL) and add dropwise sodium methoxide in methanol (25% w/v, 1.9 mL, 8.46 mmol). Stir at 70° C. overnight. Add aqueous 2 N hydrochloric acid to a pH of about 6-7 and extract with 30:70 isopropanol:chloroform. Combine the organic layers, wash with saturated aqueous sodium chloride, dry (magnesium sulphate), filter, and concentrate to give a residue. Chromatograph the residue on silica gel to give the title compound (130 mg, 41%). Dissolve the title compound in methanol and add 1 M hydrogen chloride in diethyl ether (350 μL, 0.35 mmol), triturate, and concentrate to give the hydrochloride salt of the title compound. 1H NMR (400 MHz, MeOH-d4) δ 7.96 (1H, s), 7.65-7.76 (2H, m), 7.51 (1H, dd, J=8.2, 1.6 Hz), 4.45-4.56 (2H, m), 4.17 (2H, d, J=6.4 Hz), 3.99-4.10 (2H, m), 3.85-3.95 (4H, m), 2.61 (1H, d, J=6.4 Hz), 2.39 (1H, d, J=6.1 Hz); MS (ES): m/z=371 [M+].

Workup

extractionAdd aqueous 2 N hydrochloric acid to a pH of about 6-7 and extract with 30:70 isopropanol
washwash with saturated aqueous sodium chloride
dry with materialdry (magnesium sulphate)
filtrationfilter
concentrationconcentrate
customto give a residue

Sources & evidence

ORD record: ord-e3e6cf26215b4fe8ad8fded86a1ff27c
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07868014B2

Reaction notes

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