Benzoyl chloride → 10-Benzoyl-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-C][1,4]benzodiazepine-3-carboxamide

HRID 2244270Notes

Reaction equation

HRID 2244270 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][NH:8][C:9]([C:11]2[N:20]3[C:14]([CH2:15][NH:16][C:17]4[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=4[CH2:19]3)=[CH:13][CH:12]=2)=[O:10])[CH:2]=1.C(N(CC)C(C)C)(C)C.[C:34](Cl)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>O1CCCC1>[C:34]([N:16]1[C:17]2[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=2[CH2:19][N:20]2[C:11]([C:9]([NH:8][CH2:7][C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)=[O:10])=[CH:12][CH:13]=[C:14]2[CH2:15]1)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 81531DiisopropylethylamineHCID 22053658N-(3-Pyridinylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide

Product 1

HCID 1595246810-Benzoyl-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-C][1,4]benzodiazepine-3-carboxamideYield 80.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide of Step C (300 mg, 0.942 mmol) in dry tetrahydrofuran (15 mL) at room temperature under nitrogen was added N,N-diisopropylethylamine (0.26 mL, 1.508 mmol) followed by benzoyl chloride (0.165 mL, 1.41 mmol) and the reaction mixture stirred at room temperature for 21 hours. The reaction was quenched by the addition of 2 M sodium hydroxide (5 mL) and then the mixture partitioned between ethyl acetate (50 mL) and 2 M sodium hydroxide (50 mL). The organic phase was washed with 2 M sodium hydroxide (50 mL), water (50 mL) and brine (50 mL), dried over anhydrous magnesium sulfate and concentrated in vacuo to afford a yellow syrup. Purification by flash chromatography using a solvent gradient of 0 to 4% methanol in dichloromethane gave a white foam that was crystallized from diethyl ether/hexane to give the title compound (0.319 g, 80%) as a white crystalline solid, m.p. 197° C.

Workup

  1. customThe reaction was quenched by the addition of 2 M sodium hydroxide (5 mL)
  2. customthe mixture partitioned between ethyl acetate (50 mL) and 2 M sodium hydroxide (50 mL)
  3. washThe organic phase was washed with 2 M sodium hydroxide (50 mL), water (50 mL) and brine (50 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto afford a yellow syrup
  7. customPurification by flash chromatography
  8. customgave a white foam that
  9. customwas crystallized from diethyl ether/hexane

Sources & evidence

ORD record
ord-f7afd0053d684eb28f6d3fde224c6386
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

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