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

HRID 2244295Notes

Reaction equation

HRID 2244295 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.[Cl:34][C:35]1[CH:40]=[CH:39][C:38]([CH2:41][C:42](Cl)=[O:43])=[CH:37][CH:36]=1>O1CCCC1>[Cl:34][C:35]1[CH:40]=[CH:39][C:38]([CH2:41][C:42]([N:16]2[C:17]3[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=3[CH2:19][N:20]3[C:11]([C:9]([NH:8][CH2:7][C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)=[O:10])=[CH:12][CH:13]=[C:14]3[CH2:15]2)=[O:43])=[CH:37][CH:36]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 906924-Chlorophenylacetyl chlorideHCID 22053658N-(3-Pyridinylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide

Product 1

HCID 6868775710-[(4-Chlorophenyl)acetyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-C][1,4]benzodiazepine-3-carboxamideYield 52%

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 Example 76, Step C (0.300 g, 0.942 mmol), and N,N-diisopropylethylamine (0.26 mL, 1.508 mmol) in dry tetrahydrofuran (10 mL) was added 4-chlorophenylacetyl chloride (267 mg, 1.41 mmol) and the reaction mixture stirred at room temperature under nitrogen for 21 hours. The reaction was then quenched by the addition of 2 M sodium hydroxide (5 mL) and the mixture partitioned between ethyl acetate (50 mL) and 2 M sodium hydroxide (50 mL). The organic phase was separated, washed with 2 M sodium hydroxide (50 mL), water (50 mL) and brine (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford a orange foam. Purification by flash chromatography using a solvent gradient of 0 to 4% methanol in dichloromethane gave a yellow syrup that was triturated with diethyl ether to afford the title compound 0.230 g, 52%) as a yellow solid, m.p. 83° C.

Workup

  1. customThe reaction was then 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. customThe organic phase was separated
  4. washwashed with 2 M sodium hydroxide (50 mL), water (50 mL) and brine (50 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a orange foam
  9. customPurification by flash chromatography
  10. customgave a yellow syrup that
  11. customwas triturated with diethyl ether

Sources & evidence

ORD record
ord-3639f6a40e54402a82b2a6f91a270b8d
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

Loading…