Dimethyl Sulfoxide → HCID 86730262, compound

HRID 1850211Notes

Reaction equation

HRID 1850211 reaction equation
Cl.[O:2]([C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([NH2:17])[CH3:16])=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:19]1[N:24]=[C:23]([N:25]2[CH2:29][CH2:28][O:27][C:26]2=[O:30])[C:22]([F:31])=[CH:21][N:20]=1.CCN([CH:38]([CH3:40])[CH3:39])C(C)C.[F-].[K+].[CH3:43]S(C)=O>CCOC(C)=O>[F:31][C:22]1[C:23]([N:25]2[C:29]3([CH2:39][CH2:38][CH2:40][CH2:43]3)[CH2:28][O:27][C:26]2=[O:30])=[N:24][C:19]([NH:17][C@H:15]([C:12]2[CH:11]=[CH:10][C:9]([O:2][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)=[CH:14][CH:13]=2)[CH3:16])=[N:20][CH:21]=1

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 81531Diisopropylethylamine2×HCID 522689Potassium FluorideHCID 86730263HCID 86730263, compoundHCID 86730264HCID 86730264, compound

Product 1

HCID 86730262HCID 86730262, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A solution of (S)-1-(4-phenoxyphenyl)ethanamine hydrochloride (281 mg, 1.125 mmol), 3-(2-chloro-5-fluoropyrimidin-4-yl)oxazolidin-2-one (103 mg, 0.379 mmol) and DIPEA (0.331 ml, 1.896 mmol) in DMSO was heated to 110° C. for 1 h. LCMS showed little product. Heated for an additional 16 h. LCMS still showed starting material. Added an additional 5 equivalents of DIPEA and 1 equivalent of KF. Heated to 110° C. for 2 h. LCMS shows product. The reaction mixture was diluted with EtOAc (8 mL) and washed with water (30 mL). After separation, the aqueous phase was extracted with EtOAc (3×8 mL). Combined organics were dried over Na2SO4, filtered and concentrated. Purified by column chromatography (10% to 50% EtOAc/Heptane) to give (S)-1-(5-fluoro-2-(1-(4-phenoxyphenyl)ethylamino) pyrimidin-4-yl)-3-oxa-1-azaspiro[4.4]nonan-2-one (62 mg, 0.138 mmol).

Workup

  1. temperatureHeated for an additional 16 h
  2. washwashed with water (30 mL)
  3. customAfter separation
  4. extractionthe aqueous phase was extracted with EtOAc (3×8 mL)
  5. dry with materialCombined organics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurified by column chromatography (10% to 50% EtOAc/Heptane)

Sources & evidence

ORD record
ord-0dd76266bdbc4b169ded724baa44e050
Source dataset
uspto-grants-2015_02
Patent number
US08957068B2

Reaction notes

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