Sodium Hydroxide → HCID 135985500, compound

HRID 2046004Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([C@@H:14]([N:16]3[CH2:21][CH2:20][C@@:19]([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)([CH2:22][CH2:23][CH2:24][OH:25])[O:18][C:17]3=[O:33])[CH3:15])=[CH:10][CH:9]=2)[CH:3]=1.[OH-:34].[Na+]>>[F:32][C:29]1[CH:30]=[CH:31][C:26]([C@:19]2([CH2:22][CH2:23][CH2:24][OH:25])[O:18][C:17](=[O:33])[N:16]([C@H:14]([C:11]3[CH:12]=[CH:13][C:8]([C:4]4[N:5]=[CH:6][NH:7][C:2](=[O:34])[CH:3]=4)=[CH:9][CH:10]=3)[CH3:15])[CH2:21][CH2:20]2)=[CH:27][CH:28]=1

Participants

Reactant 2

HCID 14798Sodium Hydroxide

HCID 58109473HCID 58109473, compound

Product 1

HCID 135985500HCID 135985500, compoundYield 78%

Conditions

Temperature: 110 °C

Procedure

A mixture of (R)-3-((S)-1-(4-(6-chloropyrimidin-4-yl)phenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one (20 mg, 0.0426 mmol) in 15% aq NaOH (5 mL) was heated to 110° C. overnight. Then the solvent was evaporated, and the residue was washed with EtOAc. The solid was filted off and the filtrate was dried, and condensed in vacuum to give the crude product, which was purified by preparative HPLC to afford (R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(6-oxo-1,6-dihydropyrimidin-4-yl)phenyl)ethyl)-1,3-oxazinan-2-one (15 mg, 78%). LC-MS Method 2 tR=0.91 min, m/z=452, 408. 1H NMR (CD3OD): δ=1.31 (m, 1H), 1.59 (m, 3H), 1.95 (m, 2H), 2.25 (m, 1H), 2.35 (m, 1H), 2.46 (m, 1H), 3.15 (m, 1H), 3.48 (m, 2H), 5.59 (m, 1H), 6.81 (s, 1H), 7.12 (m, 4H), 7.33 (m, 2H), 7.79 (m, 2H), 8.25 (s, 1H).

Workup

customThen the solvent was evaporated
washthe residue was washed with EtOAc
customthe filtrate was dried
customcondensed in vacuum
customto give the crude product, which
customwas purified by preparative HPLC

Sources & evidence

ORD record: ord-4e92d414189a48f896d060c784964699
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08592410B2

Reaction notes

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