Isopropanol → HCID 44204724, compound

HRID 1908251Notes

Reaction equation

F[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[C:12]([NH:14][CH2:15][C@H:16]([OH:23])[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[N:11]=[CH:10][N:9]=2)[CH:5]=[CH:4][C:3]=1[C:24](=O)[CH3:25].Cl.[NH2:28][OH:29].[OH-].[K+].C(O)(C)C>O>[CH3:25][C:24]1[C:3]2[CH:4]=[CH:5][C:6]([C:8]3[N:9]=[CH:10][N:11]=[C:12]([NH:14][CH2:15][C@@H:16]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[OH:23])[CH:13]=3)=[CH:7][C:2]=2[O:29][N:28]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 1-[2-fluoro-4-(6-{[(2R)-2-hydroxy-2-phenyl-ethyl]amino}-pyrimidin-4-yl)-phenyl]ethanone (88 mg, 0.25 mmol), hydroxylamine hydrochloride (41 mg, 0.60 mmol), KOH (85% aq., 0.158 mL), isopropanol (0.5 mL) and water (0.5 mL) was heated in a sealed tube at 90° C. for 10 h. An additional amount of KOH (85% aq., 2.38 mmol) was added and the temperature increased to 120° C. for an additional 21 h. The reaction mixture was diluted with water (5 mL) and extracted with DCM (5 mL×3). The combined extracts were dried (Na2SO4), concentrated, and the crude product purified (FCC) to yield the title compound (24 mg, 28%). MS (ESI): mass calcd. for C20H18N4O2, 346.14; m/z found, 347.2 [M+H]+. 1H NMR (CDCl3): 8.70 (d, J=0.8 Hz, 1H), 8.13 (dd, J=1.3, 0.8 Hz, 1H), 7.93 (dd, J=8.3, 1.3 Hz, 1H), 7.70 (dd, J=8.3, 0.8 Hz, 1H), 7.45-7.37 (m, 4H), 7.34-7.30 (m, 1H), 6.80 (d, J=1.0 Hz, 1H), 5.35-5.30 (m, 1H), 5.03-4.99 (m, 1H), 3.94-3.87 (m, 1H), 3.67-3.60 (m, 1H), 2.62 (s, 3H).

Workup

temperaturethe temperature increased to 120° C. for an additional 21 h
extractionextracted with DCM (5 mL×3)
dry with materialThe combined extracts were dried (Na2SO4)
concentrationconcentrated
customthe crude product purified (FCC)

Sources & evidence

ORD record: ord-b83e0f79be7f424d9b8e0a53020717c6
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598202B2

Reaction notes

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