Methanol → HCID 49833687, compound

HRID 473905Notes

Reaction equation

HRID 473905 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([N:11]2[CH2:17][C:16]3[CH:18]=[C:19]([C:22]4[CH:27]=[CH:26][C:25]([C:28]5[N:29](C(OCC(C)C)=O)[CH:30]=[CH:31][N:32]=5)=[CH:24][CH:23]=4)[CH:20]=[CH:21][C:15]=3[O:14][CH2:13][CH2:12]2)=[O:10])[CH2:5][CH2:4]1)#[N:2].CO.C1COCC1.C(=O)([O-])[O-].[K+].[K+]>O>[NH:29]1[CH:30]=[CH:31][N:32]=[C:28]1[C:25]1[CH:26]=[CH:27][C:22]([C:19]2[CH:20]=[CH:21][C:15]3[O:14][CH2:13][CH2:12][N:11]([C:9]([N:6]4[CH2:7][CH2:8][CH:3]([C:1]#[N:2])[CH2:4][CH2:5]4)=[O:10])[CH2:17][C:16]=3[CH:18]=2)=[CH:23][CH:24]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 67515133HCID 67515133, compound

Product 1

HCID 49833687HCID 49833687, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

2-Methylpropyl 2-(4-{4-[(4-cyanopiperidin-1-yl)carbonyl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}phenyl)-1H-imidazole-1-carboxylate (296 mg, 0.56 mmol) was taken into methanol (10 mL), THF (2 mL) and water (0.5 mL) then warmed to give a homogeneous solution. Potassium carbonate (160 mg, 1.15 mmol) and the mixture was stirred for 30 minutes. The mixture was then concentrated and partitioned with ethyl acetate and 10% aqueous citric acid. The organic solution was washed with brine, dried over anhydrous sodium sulfate then filtered and concentrated. The residue was purified by silica gel chromatography (10% ethanol in ethyl acetate) to give 1-({7-[4-(1H-imidazol-2-yl)phenyl]-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl}carbonyl)piperidine-4-carbonitrile (155 mg, 65% yield). 1H NMR (400 MHz, d4-methanol): 7.92 (d, 2H), 7.69 (d, 2H), 7.56 (d, 1H), 7.51 (dd, 1H), 7.15 (s, 2H), 7.04 (d, 1H), 4.51 (s, 2H), 4.21 (tr, 2H), 3.70 (tr, 2H), 3.49-3.43 (m, 2H), 3.13 (m, 2H), 2.97 (m, 1H), 1.98-1.93 (m, 2H), 1.86-1.78 (m, 2H). MS (EI) for C25H25N5O2: 429 (MH+).

Workup

  1. temperaturethen warmed
  2. customto give a homogeneous solution
  3. concentrationThe mixture was then concentrated
  4. custompartitioned with ethyl acetate and 10% aqueous citric acid
  5. washThe organic solution was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationthen filtered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography (10% ethanol in ethyl acetate)

Sources & evidence

ORD record
ord-80452160e92b4bd19fe3b6bee003c757
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

Loading…