2-Amino-1-butanol, (+)- → 4-[5-Chloro-2-(1-hydroxymethylpropylamino)-pyrimidin-4-yl]-benzoic acid methyl ester

HRID 968688Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

4-(2,5-Dichloropyrimidin-4-yl)-benzoic acid methyl ester (70 mg, 0.25 mmol) was dissolved in ethanol with 0.22 g, 2.5 mmol, of (S)-2-aminobutan-1-ol and the reaction mixture was heated to 80° C. for 6 hours, then allowed to stand at room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with 0.5 N HCl, brine, dried over sodium sulfate and concentrated to an oil, which was purified by chromatography on silica (EtOAc 20 to 60% in hexanes) to afford 4-[5-chloro-2-(1-hydroxymethylpropylamino)-pyrimidin-4-yl]-benzoic acid methyl ester as a colorless oil, 68 mg, 0.20 mmol, 80%. 1H NMR 500 MHz (CDCl3): 8.24 (s, 1H), 8.10 (d, 2H), 7.78 (d, 2H), 5.23 (m, 1H), 3.96 (m, 1H), 3.94 (s, 3H), 3.78 (m, 1H), 3.63 (m, 1H), 2.84 (br s, 1H), 1.56 (m, 2H), 0.96 (t, 3H).

Workup

washwashed with 0.5 N HCl, brine
dry with materialdried over sodium sulfate
concentrationconcentrated to an oil, which
customwas purified by chromatography on silica (EtOAc 20 to 60% in hexanes)

Sources & evidence

ORD record: ord-951c441d01ab4c2a8d936735b12345db
Source dataset: uspto-grants-2007_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07304071B2

Reaction notes

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