Potassium Carbonate → HCID 67514630, compound

HRID 473926Notes

Reaction equation

HRID 473926 reaction equation
Cl[C:2]([N:4]1[CH2:10][C:9]2[CH:11]=[C:12]([C:15]3[CH:16]=[CH:17][C:18]4[N:22]=[CH:21][N:20](C(OCC(C)C)=O)[C:19]=4[CH:30]=3)[CH:13]=[CH:14][C:8]=2[O:7][CH2:6][CH2:5]1)=[O:3].[F:31][C:32]1[CH:33]=[C:34]([CH:39]2[CH2:44][CH2:43][CH2:42][CH2:41][NH:40]2)[CH:35]=[CH:36][C:37]=1[CH3:38].[CH:45](N(C(C)C)CC)(C)C.C(=O)([O-])[O-].[K+].[K+]>CO.C1COCC1>[F:31][C:32]1[CH:33]=[C:34]([CH:39]2[CH2:44][CH2:43][CH2:42][CH2:41][N:40]2[C:2]([N:4]2[CH2:10][C:9]3[CH:11]=[C:12]([C:15]4[CH:16]=[CH:17][C:18]5[N:22]=[C:21]([CH3:45])[NH:20][C:19]=5[CH:30]=4)[CH:13]=[CH:14][C:8]=3[O:7][CH2:6][CH2:5]2)=[O:3])[CH:35]=[CH:36][C:37]=1[CH3:38]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 55297665HCID 55297665, compoundHCID 86672043HCID 86672043, compound

Product 1

HCID 67514630HCID 67514630, compoundYield 12.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Methylpropyl 6-[4-(chlorocarbonyl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazole-1-carboxylate (150 mg, 0.38 mmol) and 2-(3-fluoro-4-methylphenyl)piperidine (reagent preparation 1) (80 mg, 0.41 mmol) were taken into THF (3.5 mL) followed by addition of diisopropylethylamine (0.33 mL, 1.9 mmol) and the resulting solution was heated to reflux for 3 h. The mixture was then cooled to room temperature and partitioned with ethyl acetate and 20% aqueous citric acid. The organic phase was separated, dried over sodium sulfate then filtered and concentrated. The residue obtained was taken up into methanol (5 mL) followed by addition of solid potassium carbonate (518 mg, 3.75 mmol) and the mixture was stirred for 12 h at room temperature. The mixture was then concentrated and the residue taken into a minimum of aqueous acetonitrile and purified by preparative reverse phase HPLC. Lyophillization of the combined pure fraction afforded 4-{[2-(3-fluoro-4-methylphenyl)piperidin-1-yl]carbonyl}-7-(2-methyl-1H-benzimidazol-6-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine (23 mg) as an amorphous solid. 1H NMR (400 MHz, d6-DMSO): 12.18 (br s, 1H), 7.59 (br s, 1H), 7.47 (dd, 2H), 7.40 (d, 1H), 7.27 (dd, 1H), 7.12 (t, 1H), 7.01 (d, 1H), 6.96 (d, 2H), 4.59 (m, 1H), 4.40 (dd, 2H), 4.18 (m, 2H), 3.53 (m, 2H), 3.21 (m, 1H), 3.00 (m, 1H), 2.50 (s, 3H), 2.24 (s, 3H), 1.96 (m, 1H), 1.79 (m, 1H), 1.62-1.38 (m, 4H). MS (EI) for C30H31FN4O2: 499 (MH+).

Workup

  1. temperaturethe resulting solution was heated
  2. temperatureto reflux for 3 h
  3. custompartitioned with ethyl acetate and 20% aqueous citric acid
  4. customThe organic phase was separated
  5. dry with materialdried over sodium sulfate
  6. filtrationthen filtered
  7. concentrationconcentrated
  8. customThe residue obtained
  9. concentrationThe mixture was then concentrated
  10. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-3140fde6ce87489da9753a885439fc17
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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