Diisopropylethylamine → HCID 10157474, compound

HRID 1070422Notes

Reaction equation

HRID 1070422 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([OH:17])=O)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[CH:18]1[CH:19]=[CH:20][N:21]2[CH2:27][C:26]3[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=3[NH:24][CH2:23][C:22]=12.C(N(CC)C(C)C)(C)C>S(Cl)(Cl)=O.ClCCl>[CH:18]1[CH:19]=[CH:20][N:21]2[CH2:27][C:26]3[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=3[N:24]([C:15]([C:12]3[CH:11]=[CH:10][C:9]([C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=4)=[CH:14][CH:13]=3)=[O:17])[CH2:23][C:22]=12

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27595524'-Methoxy(1,1'-biphenyl)-4-carboxylic acidHCID 1554704810,11-Dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine

Product 1

HCID 10157474HCID 10157474, compoundYield 86.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 24386Thionyl ChlorideSolvent

Procedure

A suspension of the carboxylic acid of Step B (1.0 g, 4.38 mmol) in thionyl chloride (6 mL) was heated at reflux for 1 hour. 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 light brown solid. The acid chloride was then dissolved in dichloromethane (10 mL) and slowly added to a solution of 10,11-dihydro-5H-pyrrolo [2,1-c][1,4]benzodiazepine (1.2 g, 6.52 mmol) and N,N-diisopropylethyl amine (1.7 mL, 9.76 mmol) in dichloromethane (25 mL). After stirring for 2 hours, the reaction was quenched with water. The organic layer was washed with 1N hydrochloric acid, 1N sodium hydroxide and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow foam. Purification of the residue by flash chromatography using a solvent gradient from 15% to 50% of ethyl acetate in hexane provided the title compound (1.5 g, 86.8%) as a white solid, m.p. 187-189° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 hour
  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 light brown solid
  8. customthe reaction was quenched with water
  9. washThe organic layer was washed with 1N hydrochloric acid, 1N sodium hydroxide and brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto give a yellow foam
  14. customPurification of the residue by flash chromatography

Sources & evidence

ORD record
ord-216edd3ecfbc42ca9b660dc9aff8b70d
Source dataset
uspto-grants-2005_06
Patent number
US06903091B2

Reaction notes

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