3-Cyclopropyl-3-fluoroazetidine → HCID 178428354, compound

HRID 499087Notes

Reaction equation

HRID 499087 reaction equation
Cl[C:2]1[N:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[N:5]=[C:4]([NH:12][C:13]2[NH:17][N:16]=[C:15]([CH3:18])[CH:14]=2)[C:3]=1[F:19].[CH:20]1([C:23]2([F:27])[CH2:26][NH:25][CH2:24]2)[CH2:22][CH2:21]1>C(#N)C.C(OC(=O)C)C.O>[CH:20]1([C:23]2([F:27])[CH2:26][N:25]([C:2]3[N:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[N:5]=[C:4]([NH:12][C:13]4[NH:17][N:16]=[C:15]([CH3:18])[CH:14]=4)[C:3]=3[F:19])[CH2:24]2)[CH2:22][CH2:21]1

Participants

6

Reactant 2

HCID 576749343-Cyclopropyl-3-fluoroazetidineHCID 178428353HCID 178428353, compound

Product 1

HCID 178428354HCID 178428354, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A suspension of 6-chloro-5-fluoro-N-(3-methyl-1H-pyrazol-5-yl)-2-(methylsulfonyl)pyrimidin-4-amine (100 mg, 0.33 mmol) and 3-cyclopropyl-3-fluoroazetidine (50 mg, 0.33 mmol) in acetonitrile (5 ml) was heated to 50° C. and stirred for 1 hr. The mixture was allowed to cool and diluted with ethylacetate (20 ml) and water (20 ml). The organic layer was dried (Na2SO4) and concentrated to give a solid. Purification by flash column chromatography eluting with 40% ethylacetate/hexanes and ethyl acetate gave the title compound as an off white solid (64 mg, 51%). 1H NMR (DMSO, 400 MHz) 0.51-0.52 (2H, m), 0.68-0.76 (2H, m), 1.42-1.59 (1H, m), 2.29 (3H, s), 3.31 (3H, s), 4.20-4.36 (4H, m), 6.41 (1H, s), 9.98 (1H, s), 12.13 (1H, s). ES+ 385.

Workup

  1. temperatureto cool
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated
  4. customto give a solid
  5. customPurification by flash column chromatography
  6. washeluting with 40% ethylacetate/hexanes and ethyl acetate

Sources & evidence

ORD record
ord-b1c71b8829524031b881ea665cfab0df
Source dataset
uspto-grants-2010_08
Patent number
US07767672B2

Reaction notes

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