Triethylamine → N-[(3-{4-[(2,5-dioxoimidazolidin-4-yl)acetyl]piperazin-1-yl}phenyl)methyl]-4-oxo-3,4-dihydroquinazoline-2-carboxamide

HRID 606434Notes

Reaction equation

HRID 606434 reaction equation
Cl.Cl.[O:3]=[C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]=[C:6]([C:14]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([N:24]3[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)[CH:19]=2)=[O:15])[NH:5]1.[O:30]=[C:31]1[NH:35][CH:34]([CH2:36][C:37](O)=[O:38])[C:33](=[O:40])[NH:32]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C>[O:30]=[C:31]1[NH:35][CH:34]([CH2:36][C:37]([N:27]2[CH2:26][CH2:25][N:24]([C:20]3[CH:19]=[C:18]([CH2:17][NH:16][C:14]([C:6]4[NH:5][C:4](=[O:3])[C:13]5[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=5)[N:7]=4)=[O:15])[CH:23]=[CH:22][CH:21]=3)[CH2:29][CH2:28]2)=[O:38])[C:33](=[O:40])[NH:32]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 95492Hydantoin-5-acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 1363809654-oxo-N-[(3-piperazin-1-ylphenyl)methyl]-3,4-dihydroquinazoline-2-carboxamide dihydrochloride

Product 1

HCID 136054498N-[(3-{4-[(2,5-dioxoimidazolidin-4-yl)acetyl]piperazin-1-yl}phenyl)methyl]-4-oxo-3,4-dihydroquinazoline-2-carboxamideYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 4-oxo-N-[(3-piperazin-1-ylphenyl)methyl]-3,4-dihydroquinazoline-2-carboxamide dihydrochloride obtained in Reference Example 116 (0.109 g, 0.250 mmol), (2,5-dioxoimidazolidin-4-yl)acetic acid (0.047 g, 0.300 mmol), 1-[3-(dimethylamino)propyl]-3-ethyl-carbodiimide hydrochloride (0.096 g, 0.500 mmol) and 1-hydroxybenzotriazole (0.068 g, 0.500 mmol) in DMF (5 mL) was stirred at room temperature for 1 hr. Triethylamine (0.139 mL, 1.00 mmol) was added thereto, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC (GILSON 215LIQUD HANDLER, 322PUMP, UV/VIS-156, SHISEIDO CAPCELL PACK C-18 UG120 S-5 (20 mmφ×50 mm), mobile phase: distilled water (containing 0.1% trifluoroacetic acid)/acetonitrile (containing 0.1% trifluoroacetic acid), gradient: distilled water/acetonitrile=90/100/100, time: 10 min, flow rate: 25 mL/min, detection wavelength: 220 nm), and crystallized from methanol-diethyl ether to give the title compound as a pale-yellow powder (0.078 g, 62%).

Workup

  1. stirringthe mixture was stirred at room temperature for 12 hr
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customthe residue was purified by preparative HPLC (GILSON 215LIQUD HANDLER, 322PUMP, UV/VIS-156, SHISEIDO CAPCELL PACK C-18 UG120 S-5 (20 mmφ×50 mm), mobile phase
  4. distillationdistilled water (containing 0.1% trifluoroacetic acid)/acetonitrile (containing 0.1% trifluoroacetic acid)
  5. distillationgradient: distilled water/acetonitrile=90/100/100, time
  6. custom10 min, flow rate: 25 mL/min, detection wavelength: 220 nm), and crystallized from methanol-diethyl ether

Sources & evidence

ORD record
ord-d8b43ce22cfa4e249e9c25d3e18f4cfc
Source dataset
uspto-grants-2011_03
Patent number
US07915267B2

Reaction notes

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