Diisopropylethylamine → HCID 10110214, compound

HRID 2375151Notes

Reaction equation

HRID 2375151 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([OH:16])=O)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH:17]1[CH:18]=[CH:19][N:20]2[CH2:26][C:25]3[CH:27]=[CH:28][CH:29]=[CH:30][C:24]=3[NH:23][CH2:22][C:21]=12.C(N(CC)C(C)C)(C)C>S(Cl)(Cl)=O.ClCCl>[CH:17]1[CH:18]=[CH:19][N:20]2[CH2:26][C:25]3[CH:27]=[CH:28][CH:29]=[CH:30][C:24]=3[N:23]([C:14]([C:11]3[CH:10]=[CH:9][C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[CH:3]=4)=[CH:13][CH:12]=3)=[O:16])[CH2:22][C:21]=12

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27598163'-Methyl-biphenyl-4-carboxylic acidHCID 1554704810,11-Dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine

Product 1

HCID 10110214HCID 10110214, compoundYield 82.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 24386Thionyl ChlorideSolvent

Procedure

A suspension of 3′-methyl-[1,1′-biphenyl]-4-carboxylic acid of Step B (0.50 g, 2.36 mmol) in thionyl chloride (3 mL) was heated at reflux for 30 minutes. After cooling, the thionyl chloride was removed in vacuo. The residue was dissolved in toluene and concentrated in vacuo to give the crude acid chloride as a yellow oil. The acid chloride was then dissolved in dichloromethane (5 mL) and slowly added to a solution of the 10,11-dihydro-5H-pyrrolo [2,1-c][1,4]benzodiazepine (0.65 g, 3.53 mmol) and N,N-diisopropylethyl amine (0.90 mL, 5.17 mmol) in dichloromethane (15 mL). After stirring for 2 hours, the reaction was quenched with water. The organic layer was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine, dried over anhydrous sodium sulfate, and concentrated in vacuo to give a white foam. Purification of the residue by flash chromatography using a solvent gradient from 15% to 25% of ethyl acetate in hexane gave a white foam which was crystallized by sonication from ethyl acetate/hexane to provide the title compound (0.74 g, 82.8%) as a white solid, m.p. 128-130° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 30 minutes
  3. temperatureAfter cooling
  4. customthe thionyl chloride was removed in vacuo
  5. dissolutionThe residue was dissolved in toluene
  6. concentrationconcentrated in vacuo
  7. customto give the crude acid chloride as a yellow oil
  8. customthe reaction was quenched with water
  9. washThe organic layer was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationconcentrated in vacuo
  12. customto give a white foam
  13. customPurification of the residue by flash chromatography
  14. customgave a white foam which
  15. customwas crystallized by sonication from ethyl acetate/hexane

Sources & evidence

ORD record
ord-0a29712b81a34a7db339cc686ff7b340
Source dataset
uspto-grants-2008_12
Patent number
US07465722B2

Reaction notes

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