Ethyl Acrylate → HCID 12003965, compound

HRID 2245862Notes

Reaction equation

HRID 2245862 reaction equation
[CH2:1]([N:4]1[C@H:9]([CH3:10])[CH2:8][N:7]([C@@H:11]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([OH:33])[CH:28]=2)[C:12]2[CH:13]=[C:14]([C:18]([N:20]3[CH2:26][CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)=[O:19])[CH:15]=[CH:16][CH:17]=2)[C@@H:6]([CH3:34])[CH2:5]1)[CH:2]=[CH2:3].[C:35]([O:39][CH2:40][CH3:41])(=[O:38])[CH:36]=[CH2:37]>C(O)C>[CH2:40]([O:39][C:35](=[O:38])[CH2:36][CH2:37][N:23]1[CH2:24][CH2:25][CH2:26][N:20]([C:18](=[O:19])[C:14]2[CH:15]=[CH:16][CH:17]=[C:12]([C@@H:11]([N:7]3[CH2:8][C@@H:9]([CH3:10])[N:4]([CH2:1][CH:2]=[CH2:3])[CH2:5][C@@H:6]3[CH3:34])[C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([OH:33])[CH:28]=3)[CH:13]=2)[CH2:21][CH2:22]1)[CH3:41]

Participants

4

Reactant 2

HCID 8821Ethyl Acrylate2×HCID 58815937HCID 58815937, compound

Product 1

HCID 12003965HCID 12003965, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

The compound of Example 2 (362 mg) and ethyl acrylate (81 mg) in ethanol (10 mL) was refluxed for 4 h. TLC of reaction solution indicated a new spot and starting material. Additional ethyl acrylate (65 mg) was added to the reaction solution. The reaction was refluxed for another 6 h. After being cooled to room temperature, the reaction solution was dried by rotary evaporator. The remaining residual was purified by silica gel chromatography conducted on CombiFlash™ Sq 16× (gradient: 100% CH2Cl2 to 10% MeOH in CH2Cl2) to give 3-(4-{3-[(R)-((2S,5R)-4-allyl-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl}-[1,4]diazepan-1-yl)-propionic acid ethyl ester (275 mg; 63%). 1H NMR (300 MHz, CDCl3) δ 7.59-7.47 (m, 1H), 7.39-7.22 (m, 3H), 7.09 (m, 1H), 6.63 (m, 3H), 5.89 (m, 1H), 5.21 (m, 3H), 4.14 (q, 2H, J=7.0 Hz), 3.76-3.63 (m, 2H), 3.44-3.34 (m, 3H), 2.95-2.76 (m, 5H), 2.72-2.39 (m, 8H), 2.17 (dd, 1H, J=10.0, 10.0 Hz), 2.00 (dd, 1H, J=11.0, 11.0 Hz), 1.92 (m, 1H), 1.69 (m, 1H), 1.25 (t, 3H, J=7.0 Hz), 1.15 (d, 3H, J=6.0 Hz), 1.02 (d, 3H, J=5.5 Hz); MS (FAB, glycerol) m/z: 563 (M++1), 409, 209, 153; Found C, 68.59; H, 8.30; N, 9.64. Calc. (C33H46N4O4 0.2 CH2Cl2) C, 68.78; H, 8.07; N, 9.66.

Workup

  1. customTLC of reaction solution
  2. temperatureThe reaction was refluxed for another 6 h
  3. customthe reaction solution was dried by rotary evaporator
  4. customThe remaining residual was purified by silica gel chromatography

Sources & evidence

ORD record
ord-0753ea27f24a4bdaa9de4e9603cd4fb2
Source dataset
uspto-grants-2010_03
Patent number
US07683168B2

Reaction notes

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