Oxalyl chloride → HCID 21947709, compound

HRID 2215153Notes

Reaction equation

HRID 2215153 reaction equation
[CH3:1][C:2]1[N:3]([C:8]2[C:16]([CH3:17])=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][C:9]=2[CH3:18])[C:4]([CH3:7])=[CH:5][CH:6]=1.C(Cl)(=O)C(Cl)=O.[CH:25]1[CH:26]=[CH:27][N:28]2[CH2:34][C:33]3[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=3[NH:31][CH2:30][C:29]=12.CCN(C(C)C)C(C)C>O1CCCC1.ClCCl.CN(C)C=O>[CH3:7][C:4]1[N:3]([C:8]2[C:9]([CH3:18])=[CH:10][C:11]([C:12]([N:31]3[C:32]4[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=4[CH2:34][N:28]4[CH:27]=[CH:26][CH:25]=[C:29]4[CH2:30]3)=[O:14])=[CH:15][C:16]=2[CH3:17])[C:2]([CH3:1])=[CH:6][CH:5]=1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 1554704810,11-Dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepineHCID 21947752HCID 21947752, compound

Product 1

HCID 21947709HCID 21947709, compoundYield 15.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-(2,5-dimethyl-1H-pyrrol-1-yl)-3,5-dimethylbenzoic acid of Step B (0.495 g, 2 mmol) was dissolved in tetrahydrofuran (10 mL) and treated with N,N-dimethylformamide (10 μL) followed by oxalyl chloride (250 μL, 2.85 mmol) added dropwise to control gas evolution. When the gas evolution subsided, the solution was warmed to reflux for 5 minutes. The solution was then concentrated in vacuo, the residue was dissolved in tetrahydrofuran and evaporated to dryness. The residue was redissolved in dichloromethane and the solution added dropwise to a cold solution (0° C.) of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.372mg, 2 mmol) and Hünig's base (0.5 mL) in dichloromethane. The solution was stirred overnight at room temperature, washed successively with 1N hydrochloric acid, saturated aqueous bicarbonate, and brine. The sample was then dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to a yellow foam (0.75 g). Flash chromatography of this material on silica gel eluting with a solvent gradient of 10 to 20% of ethyl acetate in hexane, provided a white solid (0.130 g). Recrystallization of this material from ethyl acetate/hexane provided the title compound (0.120 g) as flat crystals, m.p. 197–199° C.

Workup

  1. additionadded dropwise
  2. temperaturethe solution was warmed
  3. temperatureto reflux for 5 minutes
  4. concentrationThe solution was then concentrated in vacuo
  5. dissolutionthe residue was dissolved in tetrahydrofuran
  6. customevaporated to dryness
  7. dissolutionThe residue was redissolved in dichloromethane
  8. washwashed successively with 1N hydrochloric acid, saturated aqueous bicarbonate, and brine
  9. dry with materialThe sample was then dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. customevaporated in vacuo to a yellow foam (0.75 g)

Sources & evidence

ORD record
ord-5645b189db3c4395bd3ac95569a3bbe6
Source dataset
uspto-grants-2006_09
Patent number
US07109193B2

Reaction notes

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