Hydrochloric Acid → 3-Cyclopropyl-3-(6-((5-((5,5-dimethyltetrahydrofuran-3-yl)methoxy)-6-(2-fluoro-5-methoxyphenyl)pyridin-3-yl)methoxy)pyrimidin-4-yl)propanoic acid

HRID 709804Notes

Reaction equation

HRID 709804 reaction equation
[CH3:1][C:2]1([CH3:26])[O:6][CH2:5][CH:4]([CH2:7][O:8][C:9]2[CH:10]=[C:11]([CH2:24][OH:25])[CH:12]=[N:13][C:14]=2[C:15]2[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:16]=2[F:23])[CH2:3]1.Cl[C:28]1[N:33]=[CH:32][N:31]=[C:30]([CH:34]([CH:41]2[CH2:43][CH2:42]2)[CH2:35][C:36]([O:38]CC)=[O:37])[CH:29]=1.[H-].[Na+].Cl>C1COCC1>[CH:41]1([CH:34]([C:30]2[CH:29]=[C:28]([O:25][CH2:24][C:11]3[CH:12]=[N:13][C:14]([C:15]4[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:16]=4[F:23])=[C:9]([O:8][CH2:7][CH:4]4[CH2:3][C:2]([CH3:26])([CH3:1])[O:6][CH2:5]4)[CH:10]=3)[N:33]=[CH:32][N:31]=2)[CH2:35][C:36]([OH:38])=[O:37])[CH2:43][CH2:42]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 117760030Ethyl 3-(6-chloropyrimidin-4-yl)-3-cyclopropylpropanoateHCID 117760261(5-((5,5-Dimethyltetrahydrofuran-3-yl)methoxy)-6-(2-fluoro-5-methoxyphenyl)pyridin-3-yl)methanol

Product 1

HCID 1177602663-Cyclopropyl-3-(6-((5-((5,5-dimethyltetrahydrofuran-3-yl)methoxy)-6-(2-fluoro-5-methoxyphenyl)pyridin-3-yl)methoxy)pyrimidin-4-yl)propanoic acidYield 14.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (5-((5,5-dimethyltetrahydrofuran-3-yl)methoxy)-6-(2-fluoro-5-methoxyphenyl)pyridin-3-yl)methanol (180 mg) and ethyl 3-(6-chloropyrimidin-4-yl)-3-cyclopropylpropanoate (140 mg) in THF (5.0 mL) was slowly added 60% sodium hydride (60 mg) at 0° C. by small portions, and the mixture was stirred at 50° C. for 3 hr. The mixture was acidified with 1N hydrochloric acid at 0° C. and extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by preparative HPLC (C18, mobile phase: water/acetonitrile (10 mM NH4HCO3-containing system)), and the obtained fraction was evaporated under reduced pressure to give the title compound (40 mg) as a white solid.

Workup

  1. customat 0° C.
  2. extractionextracted with ethyl acetate
  3. dry with materialThe extract was dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by preparative HPLC (C18, mobile phase: water/acetonitrile (10 mM NH4HCO3-containing system))
  6. customthe obtained fraction was evaporated under reduced pressure

Sources & evidence

ORD record
ord-4bd717bda2a246b8b4a11decca86be36
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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