Triethylamine → (S)-4-(4-(1,6-dihydro-1-methyl-6-oxo-4-(pyrimidin-4-yl)pyrimidin-2-yl)-[1,4]oxazepan-6-yl)benzonitrile

HRID 515467Notes

Reaction equation

HRID 515467 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][N:11]=2)[N:3]=1.[O:16]1[CH2:22][C@@H:21]([C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=2)[CH2:20][NH:19][CH2:18][CH2:17]1.C(N(CC)CC)C>>[CH3:8][N:7]1[C:6](=[O:9])[CH:5]=[C:4]([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][N:11]=2)[N:3]=[C:2]1[N:19]1[CH2:20][C@H:21]([C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=2)[CH2:22][O:16][CH2:17][CH2:18]1

Participants

4

Reactant 3

HCID 8471TriethylamineHCID 179544602-Chloro-3-methyl-6-(pyrimidin-4-YL)pyrimidin-4-oneHCID 67281424(S)-4-([1,4]oxazepan-6-yl)benzonitrile

Product 1

HCID 46935963(S)-4-(4-(1,6-dihydro-1-methyl-6-oxo-4-(pyrimidin-4-yl)pyrimidin-2-yl)-[1,4]oxazepan-6-yl)benzonitrileYield 73.2%

Procedure

To a solution of 2-chloro-3-methyl-6-(pyrimidin-4-yl)-3H-pyrimidin-4-one (73.4 mg, 0.330 mmol) and (S)-4-([1,4]oxazepan-6-yl)benzonitrile (70.0 mg, 0.346 mmol) was added triethylamine (100 mg, 0.989 mmol) at room temperature. The mixture was stirred at room temperature for 5 hours and partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=1/9) to afford (S)-4-(4-(1,6-dihydro-1-methyl-6-oxo-4-(pyrimidin-4-yl)pyrimidin-2-yl)-[1,4]oxazepan-6-yl)benzonitrile (A076) as white solid (93.8 mg, 70%).

Workup

  1. custompartitioned between water and ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=1/9)

Sources & evidence

ORD record
ord-da329072c6e8402c8c7079d7bd4b2899
Source dataset
uspto-grants-2015_08
Patent number
US09108957B2

Reaction notes

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