1-Butanol → N-[1-(3-cyano-4,6-dimethylpyridin-2-yl)azetidin-3-yl]-2-(3-fluorophenyl)pyrimidine-5-carboxamide

HRID 563860Notes

Reaction equation

[NH:1]1[CH2:4][CH:3]([NH:5][C:6]([C:8]2[CH:9]=[N:10][C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=3)=[N:12][CH:13]=2)=[O:7])[CH2:2]1.Cl[C:22]1[N:29]=[C:28]([CH3:30])[CH:27]=[C:26]([CH3:31])[C:23]=1[C:24]#[N:25].C(O)CCC.O>C(OCC)(=O)C.[Cl-].[Na+].O>[C:24]([C:23]1[C:22]([N:1]2[CH2:4][CH:3]([NH:5][C:6]([C:8]3[CH:13]=[N:12][C:11]([C:14]4[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=4)=[N:10][CH:9]=3)=[O:7])[CH2:2]2)=[N:29][C:28]([CH3:30])=[CH:27][C:26]=1[CH3:31])#[N:25]

Participants

Conditions

Temperature: 90 °C

Procedure

To a vial was added N-azetidin-3-yl-2-(3-fluorophenyl)pyrimidine-5-carboxamide (0.04 g, 0.13 mmol), 2-chloro-4,6-dimethylnicotinonitrile (32.5 mg, 0.19 mmol), and 0.3 mL each of n-butanol, TEA and water. The mixture was heated to 90° C. for 12 hrs and then diluted with ethyl acetate and brine. The layers were separated and the organic layer dried (Na2SO4) and the solvent removed to give a solid, which was purified by chromatography (silica, DCM to 1-5% MeOH/DCM) to give the product, N-[1-(3-cyano-4,6-dimethylpyridin-2-yl)azetidin-3-yl]-2-(3-fluorophenyl)pyrimidine-5-carboxamide (52 mg, 76%). HRMS (M+H)=403.1682 expected, 403.1750 observed.

Workup

customThe layers were separated
dry with materialthe organic layer dried (Na2SO4)
customthe solvent removed
customto give a solid, which
customwas purified by chromatography (silica, DCM to 1-5% MeOH/DCM)

Sources & evidence

ORD record: ord-22a40ed410854998a3d7655641efaba2
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08067589B2

Reaction notes

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