Carbon Tetrachloride → benzyl(3-(benzyloxy)-2-(4-chloro-5-(4-fluorobenzyl)-1H-imidazol-2-yl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)carbamate

HRID 80690Notes

Reaction equation

HRID 80690 reaction equation
[CH2:1]([O:8][C:9](=[O:47])[NH:10][C:11]12[CH2:19][CH2:18][CH:15]([CH2:16][CH2:17]1)[CH2:14][N:13]1[C:20](=[O:46])[C:21]([O:38][CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[C:22]([C:24](=O)[NH:25][CH:26]([C:35]#[N:36])[CH2:27][C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[N:23]=[C:12]21)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(Cl)(Cl)[Cl:49].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(#N)C>[CH2:1]([O:8][C:9](=[O:47])[NH:10][C:11]12[CH2:17][CH2:16][CH:15]([CH2:18][CH2:19]1)[CH2:14][N:13]1[C:20](=[O:46])[C:21]([O:38][CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[C:22]([C:24]3[NH:25][C:26]([CH2:27][C:28]4[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=4)=[C:35]([Cl:49])[N:36]=3)[N:23]=[C:12]21)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 5943Carbon TetrachlorideHCID 11776TriphenylphosphineHCID 117616854Benzyl(3-(benzyloxy)-2-((1-cyano-2-(4-fluorophenyl)ethyl)carbamoyl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)carbamate

Product 1

HCID 117616853benzyl(3-(benzyloxy)-2-(4-chloro-5-(4-fluorobenzyl)-1H-imidazol-2-yl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)carbamateYield 42%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of benzyl(3-(benzyloxy)-2-((1-cyano-2-(4-fluorophenyl)ethyl)carbamoyl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)carbamate, Intermediate 5 (140 mg, 0.220 mmol) in acetonitrile (4 mL) was added carbon tetrachloride (0.053 mL, 0.551 mmol), followed by triphenylphosphine (144 mg, 0.551 mmol) and the mixture was heated at 45° C. After stirring for 16 h, the mixture was cooled to room temp and concentrated in vacuo. The residue was then treated with dichloromethane (10 mL) and 0.5 N NaOH (20 mL). The mixture was then poured into water and extracted with dichloromethane (×4), dried (Na2SO4), filtered and concentrated. The crude product was then purified by silica gel chromatography (40-100% EtOAc/hexane) to afford the title compound (90 mg, 42% yield) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ ppm 1.65-1.74 (m, 2H) 1.92-2.03 (m, 4H) 2.47 (br. s., 1H) 2.71-2.86 (m, 2H) 3.74 (s, 2H) 4.13 (d, J=3.66 Hz, 2H) 5.12 (s, 2H) 5.29 (s, 2H) 6.92 (d, J=7.63 Hz, 4H) 7.08 (br. s., 1H) 7.29-7.37 (m, 8H) 7.39-7.46 (m, 2H) 10.08 (br. s., 1H). (M+H)=654.28.

Workup

  1. temperaturethe mixture was cooled to room temp
  2. concentrationconcentrated in vacuo
  3. additionThe residue was then treated with dichloromethane (10 mL) and 0.5 N NaOH (20 mL)
  4. additionThe mixture was then poured into water
  5. extractionextracted with dichloromethane (×4)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was then purified by silica gel chromatography (40-100% EtOAc/hexane)

Sources & evidence

ORD record
ord-bc7e3926d68944b58083f5dded589665
Source dataset
uspto-grants-2014_09
Patent number
US08846659B2

Reaction notes

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