Diisopropylethylamine → (4-Iodo-2-methoxyphenyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylmethanone

HRID 1830078Notes

Reaction equation

HRID 1830078 reaction equation
[I:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([O:11][CH3:12])[CH:3]=1.[CH:13]1[CH:14]=[CH:15][N:16]2[CH2:22][C:21]3[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=3[NH:19][CH2:18][C:17]=12.C(N(CC)C(C)C)(C)C>S(Cl)(Cl)=O.ClCCl>[I:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:19]2[C:20]3[CH:26]=[CH:25][CH:24]=[CH:23][C:21]=3[CH2:22][N:16]3[CH:15]=[CH:14][CH:13]=[C:17]3[CH2:18]2)=[O:8])=[C:4]([O:11][CH3:12])[CH:3]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 134507564-Iodo-2-methoxybenzoic acidHCID 1554704810,11-Dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine

Product 1

HCID 21947920(4-Iodo-2-methoxyphenyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylmethanoneYield 90%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 24386Thionyl ChlorideSolvent

Procedure

A suspension of 4-iodo-2-methoxybenzoic acid of Step B (2.5 g, 9.0 mmol) in thionyl chloride (10 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 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 (1.75 g, 9.5 mmol) and N,N-diisopropylethyl amine (3.4 mL, 19.5 mmol) in dichloromethane (20 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, filtered and concentrated in vacuo to give a yellow foam. Purification by flash chromatography on silica gel using a solvent gradient of 15 to 25% ethyl acetate in hexane provided 3.6 g of title product as a white foam, which was redissolved in dichloromethane and evaporated to dryness prior to use in the next step.

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 brown solid
  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. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto give a yellow foam
  14. customPurification by flash chromatography on silica gel using a solvent gradient of 15 to 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-ee02327a31024d679fb642bb6ef074a6
Source dataset
uspto-grants-2006_06
Patent number
US07064120B2

Reaction notes

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