Phosgene → HCID 67515133, compound

HRID 473904Notes

Reaction equation

HRID 473904 reaction equation
[O:1]1[C:7]2[CH:8]=[CH:9][C:10]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4[N:19]([C:23]([O:25][CH2:26][CH:27]([CH3:29])[CH3:28])=[O:24])[CH:20]=[CH:21][N:22]=4)=[CH:14][CH:13]=3)=[CH:11][C:6]=2[CH2:5][NH:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[C:39](Cl)(Cl)=[O:40].Cl.[C:44]([CH:46]1[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1)#[N:45]>ClCCl>[C:44]([CH:46]1[CH2:51][CH2:50][N:49]([C:39]([N:4]2[CH2:5][C:6]3[CH:11]=[C:10]([C:12]4[CH:13]=[CH:14][C:15]([C:18]5[N:19]([C:23]([O:25][CH2:26][CH:27]([CH3:29])[CH3:28])=[O:24])[CH:20]=[CH:21][N:22]=5)=[CH:16][CH:17]=4)[CH:9]=[CH:8][C:7]=3[O:1][CH2:2][CH2:3]2)=[O:40])[CH2:48][CH2:47]1)#[N:45]

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 81531Diisopropylethylamine2×HCID 227446374-Piperidinecarbonitrile hydrochlorideHCID 67513954HCID 67513954, compound

Product 1

HCID 67515133HCID 67515133, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

2-methylpropyl 2-[4-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)phenyl]-1H-imidazole-1-carboxylate (361 mg, 0.92 mmol) was taken into dichloromethane (5 mL) followed by addition of DIPEA (0.32 mL, 1.84 mmol). The solution thus obtained was added slowly by syringe over several minutes to a solution of phosgene (20 W % in toluene, 0.49 mL, 0.93 mmol) diluted in dichloromethane (5 mL) and cooled to 0° C. The resulting mixture was stirred for 5 minutes then allowed to warm to room temperature and concentrated. The residue was taken back into dichloromethane (5 mL) followed by addition of DIPEA (0.48 mL, 2.76 mmol) and 4-cyanopiperidine hydrochloride salt (156 mg, 1.06 mmol) then stirred for 12 h. The mixture was concentrated then 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 (100% ethyl acetate) to give 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, 61% yield) as a crystalline solid. MS (EI) for C30H33N5O4: 529 (MH+).

Workup

  1. customThe solution thus obtained
  2. temperatureto warm to room temperature
  3. concentrationconcentrated
  4. stirringthen stirred for 12 h
  5. concentrationThe mixture was concentrated
  6. customthen partitioned with ethyl acetate and 10% aqueous citric acid
  7. washThe organic solution was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationthen filtered
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel chromatography (100% ethyl acetate)

Sources & evidence

ORD record
ord-1f6edd0b9e5248709d61f42edf95c663
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

Loading…