Phenyl isocyanate → HCID 9829666, compound

HRID 482354Notes

Reaction equation

HRID 482354 reaction equation
Br.Br.[NH2:3][CH:4]1[C:10](=[O:11])[N:9]([CH2:12][C:13]([N:15]([CH:24]([CH3:26])[CH3:25])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)=[O:14])[C:8]2[CH:27]=[CH:28][CH:29]=[CH:30][C:7]=2[C:6]([C:31]2[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=2)=[N:5]1.C(N(CC)CC)C.[C:44]1([N:50]=[C:51]=[O:52])[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C(Cl)Cl>[CH:24]([N:15]([C:16]1[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=1)[C:13](=[O:14])[CH2:12][N:9]1[C:8]2[CH:27]=[CH:28][CH:29]=[CH:30][C:7]=2[C:6]([C:31]2[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=2)=[N:5][CH:4]([NH:3][C:51]([NH:50][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[O:52])[C:10]1=[O:11])([CH3:26])[CH3:25]

Participants

5

Reactant 3

HCID 7672Phenyl isocyanateHCID 8471TriethylamineHCID 19063691HCID 19063691, compound

Product 1

HCID 9829666HCID 9829666, compoundYield 58.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

According to process A, a solution of 175 mg of 2-(3-amino-2-oxo-5-pyridin-3-yl-2,3-dihydro-benzo[e][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide dihydrobromide (0.283 mmol), prepared as in Intermediate 31, in 3 mL of methylene chloride was treated with 98.5 μL of triethylamine (0.706 mmol) and 33.8 μL of phenyl isocyanate (0.311 mmol). After stirring under nitrogen for 20 min., the reaction mixture was diluted with methylene chloride and washed with aqueous potassium carbonate (5% w/v). The phases were separated and the organic layer was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to a residue. The residue was triturated with 5 mL of acetonitrile and the resulting slurry was heated to reflux under nitrogen. After stirring for 20 min., the slurry was cooled to ambient temperature, filtered and washed with cold acetonitrile. The product was combined again with 3 mL of acetonitrile and brought to reflux. After stirring for 30 min., the slurry was cooled to ambient temperature, filtered and washed with cold acetonitrile. The product was dried under high vacuum to provide 95 mg of the title compound as a white crystalline solid. 1H NMR (300 MHz, d6-DMSO) -- =9.06 (b, 1H), 8.68 (m, 2H), 7.93 (d, 1H, J=8.0), 7.72 (m, 1H), 7.53 (m, 3H), 7.37 (m, 4H), 7.26 (m, 4H), 7.07 (m, 2H), 6.94 (m, 1H), 5.31 (d, 1H, J=8.3), 4.72 (m, 1H), 4.29 (d, 1H, J=16.4), 4.16 (d, 1H, J=16.4), 3.81 (s, 3H), 0.96 (d, 6H, J=6.1); MS (ESI) [M+H]+ =577.

Workup

  1. washwashed with aqueous potassium carbonate (5% w/v)
  2. customThe phases were separated
  3. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo to a residue
  6. customThe residue was triturated with 5 mL of acetonitrile
  7. temperaturethe resulting slurry was heated
  8. temperatureto reflux under nitrogen
  9. stirringAfter stirring for 20 min.
  10. filtrationfiltered
  11. washwashed with cold acetonitrile
  12. temperatureto reflux
  13. stirringAfter stirring for 30 min.
  14. temperaturethe slurry was cooled to ambient temperature
  15. filtrationfiltered
  16. washwashed with cold acetonitrile
  17. customThe product was dried under high vacuum

Sources & evidence

ORD record
ord-2aba0ce3a7cc42ba88488f2a91dc4fba
Source dataset
uspto-grants-1998_08
Patent number
US05795887

Reaction notes

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