Diisopropylethylamine → HCID 68687725, compound

HRID 2244296Notes

Reaction equation

HRID 2244296 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:43])/[CH:35]=[CH:36]/[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>O1CCCC1>[C:37]1(/[CH:36]=[CH:35]/[C:34]([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:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5354261Cinnamoyl ChlorideHCID 22053658N-(3-Pyridinylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide

Product 1

HCID 68687725HCID 68687725, compoundYield 85.2%

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 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 trans-cinnamoyl chloride (0.235 g, 1.41 mmol) and the reaction mixture was 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, and concentrated in vacuo to afford a yellow foam. Purification by flash chromatography using a solvent gradient of 1 to 4% methanol in dichloromethane gave a yellow syrup that was crystallized from diethyl ether/ethyl acetate/hexane to afford the title compound (0.360 g, 85%) as an off-white solid, m.p. 175° 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. concentrationconcentrated in vacuo
  7. customto afford a yellow foam
  8. customPurification by flash chromatography
  9. customgave a yellow syrup that
  10. customwas crystallized from diethyl ether/ethyl acetate/hexane

Sources & evidence

ORD record
ord-07a64a95a9f54c0a9d527888d6a511a2
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

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