Triethylamine → 2-((2S)-2-(4-(N-((3R)-tetrahydrofuran-3-yl)amino)phenyl)-morpholin-4-yl)-3-methyl-6-(3-fluoropyridin-4-yl)-3H-pyrimidin-4-one

HRID 1091405Notes

Reaction equation

Cl[C:2]1[N:7]([CH3:8])[C:6](=[O:9])[CH:5]=[C:4]([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][C:11]=2[F:16])[N:3]=1.[O:17]1[CH2:21][CH2:20][C@@H:19]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([C@@H:29]3[O:34][CH2:33][CH2:32][NH:31][CH2:30]3)=[CH:25][CH:24]=2)[CH2:18]1.C(N(CC)CC)C>O1CCCC1>[O:17]1[CH2:21][CH2:20][C@@H:19]([NH:22][C:23]2[CH:24]=[CH:25][C:26]([C@@H:29]3[O:34][CH2:33][CH2:32][N:31]([C:2]4[N:7]([CH3:8])[C:6](=[O:9])[CH:5]=[C:4]([C:10]5[CH:15]=[CH:14][N:13]=[CH:12][C:11]=5[F:16])[N:3]=4)[CH2:30]3)=[CH:27][CH:28]=2)[CH2:18]1

Participants

Conditions

Temperature: 95 °C

Procedure

A solution of 2-chloro-6-(3-fluoropyridin-4-yl)-3-methyl-3H-pyrimidin-4-one (0.08 g, 0.35 mmol), (2S)-2-(4-(N-((3R)-tetrahydrofuran-3-yl)amino)phenyl)morpholine obtained in Reference Example 7 (0.11 g, 0.44 mmol) and triethylamine (0.22 g, 2.2 mmol) in tetrahydrofuran (10 ml) was stirred at 95° C. for 3 hours. The mixture was partitioned between water and dichloromethane, and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting 5-10% methanol in chloroform to furnish 2-((2S)-2-(4-(N-((3R)-tetrahydrofuran-3-yl)amino)phenyl)-morpholin-4-yl)-3-methyl-6-(3-fluoropyridin-4-yl)-3H-pyrimidin-4-one (0.07 g, 47%) as pale yellow crystals.

Workup

customThe mixture was partitioned between water and dichloromethane
washthe organic layer was washed with brine
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by silica gel column chromatography
washeluting 5-10% methanol in chloroform

Sources & evidence

ORD record: ord-7ff887a523c9493f8020d22c1f5f36c7
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129377B2

Reaction notes

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