Sodium Hydroxide → HCID 178461658, compound

HRID 2037732Notes

Reaction equation

HRID 2037732 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[CH:3]=[C:2]([OH:34])[N:7]=[CH:6][N:5]=4)=[CH:9][CH:10]=3)[CH3:15])[CH2:21][CH2:20]2)=[CH:27][CH:28]=1

Participants

3

Reactant 2

HCID 14798Sodium HydroxideHCID 58109473HCID 58109473, compound

Product 1

HCID 178461658HCID 178461658, 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-hydroxypyrimidin-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

  1. customThen the solvent was evaporated
  2. washthe residue was washed with EtOAc
  3. customthe filtrate was dried
  4. customcondensed in vacuum
  5. customto give the crude product, which
  6. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-56f60bd7ee804f0cbf6a2cd184d1505c
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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