Propanedioyl dichloride → 2-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide

HRID 343091

Reaction equation

HRID 343091 reaction equation
[CH:1]([N:4]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1)[C:5](=[O:21])[CH2:6][NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([CH3:3])[CH3:2].[C:30](Cl)(=[O:35])[CH2:31][C:32](Cl)=[O:33]>C1COCC1>[O:33]=[C:32]1[N:7]([CH2:6][C:5]([N:4]([CH:1]([CH3:3])[CH3:2])[C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)=[O:21])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[N:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:30](=[O:35])[CH2:31]1

Participants

4

Reactant 2

HCID 74269Propanedioyl dichlorideHCID 10644060N-Isopropyl-N-(4-methoxy-phenyl)-2-(2-phenylamino-phenylamino)-acetamide

Product 1

HCID 107900232-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamideYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To 100 mL of THF at 0° C. is added dropwise over 20 min simultaneously a solution of 8.0 g (20.5 mmol) of N-isopropyl-N-(4-methoxy-phenyl)-2-(2-phenylamino-phenylamino) acetamide, prepared as in Intermediate 43, in 100 mL of THF and 2.40 mL (24.6 mmol, 1.2 equiv) of malonyl dichloride in 100 mL of THF. The resulting solution is stirred at RT for 20 h and the solvent removed in vacuo. Purification of the resulting brown oil by silica gel flash column chromatography afforded 7.5 g of the title compound as a light tan solid: 1H NMR (CDCl3, 300 MHz) δ7.44-6.86 (m, 13H), 5.02 (m, 1H), 4.38 (d, 1H, J=16.6), 4.04 (d, 1H, J=16.6), 3.84 (s, 3H), 2.55 (m, 2H), 1.10 (d, 6H, J=6.8); Rf =0.15 in hexane/EtOAc 1/1.

Workup

  1. customthe solvent removed in vacuo
  2. customPurification of the resulting brown oil by silica gel flash column chromatography

Sources & evidence

ORD record
ord-94680beec9724515a4acf4ad12aa42fc
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Linked notes

Loading…