Sodium Hydroxide → HCID 71466082, compound

HRID 572662Notes

Reaction equation

HRID 572662 reaction equation
C([O:4][CH2:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:18][N:17]=[C:16]([C:19]3[CH:24]=[C:23]([C:25](=[O:37])[NH:26][CH2:27][C:28]4[CH:33]=[CH:32][C:31]([F:34])=[C:30]([O:35][CH3:36])[CH:29]=4)[N:22]=[C:21]([CH3:38])[N:20]=3)[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])(=O)C.[OH-].[Na+]>C(#N)C>[F:34][C:31]1[CH:32]=[CH:33][C:28]([CH2:27][NH:26][C:25]([C:23]2[CH:24]=[C:19]([C:16]3[CH2:15][CH:14]([CH:11]4[CH2:10][CH2:9][N:8]([C:6](=[O:7])[CH2:5][OH:4])[CH2:13][CH2:12]4)[O:18][N:17]=3)[N:20]=[C:21]([CH3:38])[N:22]=2)=[O:37])=[CH:29][C:30]=1[O:35][CH3:36]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86675917HCID 86675917, compound

Product 1

HCID 71466082HCID 71466082, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-(4-(3-(6-(4-Fluoro-3-methoxybenzylcarbamoyl)-2-methylpyrimidin-4-yl)-4,5-dihydroisoxazol-5-yl)piperidin-1-yl)-2-oxoethyl acetate (1.8 g, 3.5 mmol) was dissolved in ACN (20 mL) and 2.5 N sodium hydroxide (20 mL) was added. The mixture was stirred for about 6 h and then ACN was removed under reduced pressure. The aqueous layer was adjusted to pH 6 with 10% aqueous hydrogen chloride and then extracted with EtOAc (2×15 mL). The combined organic layers were dried over sodium sulphate and concentrated under reduced pressure. The crude material was purified by preparative HPLC (Table 2, Method a) to afford N-(4-fluoro-3-methoxybenzyl)-6-(5-(1-(2-hydroxyacetyl)piperidin-4-yl)-4,5-dihydroisoxazol-3-yl)-2-methylpyrimidine-4-carboxamide 0.65 g (39%): 1H NMR (400 MHz, DMSO): δ 9.499-9.467 (t, J=6.4 Hz, 1H), 8.139 (s, 1H), 7.143-7.114 (m, 2H), 6.900-6.884 (m, 1H), 4.684-4.657 (m, 1H), 4.482-4.38 (m, 4H), 4.095-4.049 (m, 3H), 3.815 (s, 3H), 3.495-3.451 (m, 1H), 3.217-3.196 (m, 2H), 2.911-2.800 (m, 1H), 2.752 (s, 3H), 1.855-1.684 (m, 3H), 1.234-1.105 (m, 2H). LC/MS Rt=1.22 (Table 1, method c) min; MS m/z: 486.3 (M+H)+.

Workup

  1. customACN was removed under reduced pressure
  2. extractionextracted with EtOAc (2×15 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material was purified by preparative HPLC (Table 2, Method a)

Sources & evidence

ORD record
ord-eec500a7d01b44f0a2f7cad958b389cb
Source dataset
uspto-grants-2015_05
Patent number
US09029409B2

Reaction notes

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