1-Hydroxybenzotriazole → N-({4'-[({1-[(hydroxyamino)carbonyl]-2-methylpropyl}amino)sulfonyl]biphenyl-3-yl}methyl)-4-oxo-3,4-dihydroquinazoline-2-carboxamide

HRID 606429Notes

Reaction equation

HRID 606429 reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([NH:14][CH2:15][C:16]2[CH:17]=[C:18]([C:22]3[CH:27]=[CH:26][C:25]([S:28]([NH:31][C@H:32]([C:36](O)=[O:37])[CH:33]([CH3:35])[CH3:34])(=[O:30])=[O:29])=[CH:24][CH:23]=3)[CH:19]=[CH:20][CH:21]=2)=[O:13])[NH:3]1.C[Si](C)(C)[O:41][NH2:42].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C=O)C.C(OCC)(=O)C>[OH:41][NH:42][C:36]([CH:32]([NH:31][S:28]([C:25]1[CH:26]=[CH:27][C:22]([C:18]2[CH:19]=[CH:20][CH:21]=[C:16]([CH2:15][NH:14][C:12]([C:4]3[NH:3][C:2](=[O:1])[C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[N:5]=3)=[O:13])[CH:17]=2)=[CH:23][CH:24]=1)(=[O:29])=[O:30])[CH:33]([CH3:34])[CH3:35])=[O:37]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 136380958N-{[3'-({[(4-oxo-3,4-dihydroquinazolin-2-yl)carbonyl]amino}methyl)biphenyl-4-yl]sulfonyl}valine

Product 1

HCID 136054465N-({4'-[({1-[(hydroxyamino)carbonyl]-2-methylpropyl}amino)sulfonyl]biphenyl-3-yl}methyl)-4-oxo-3,4-dihydroquinazoline-2-carboxamideYield 71%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of N-{[3′-({[(4-oxo-3,4-dihydroquinazolin-2-yl)carbonyl]amino}methyl)biphenyl-4-yl]sulfonyl}valine obtained in Example 77 (0.080 g, 0.150 mmol), O-(trimethylsilyl)hydroxylamine (0.055 mL, 0.449 mmol), 1-[3-(dimethylamino)propyl]-3-ethyl-carbodiimide hydrochloride (0.086 g, 0.449 mmol) and 1-hydroxybenzotriazole (0.061 g, 0.449 mmol) in DMF (5 mL) was stirred at room temperature for 12 hr. The reaction mixture was diluted with ethyl acetate, and washed successively with 0.05N hydrochloric acid, aqueous sodium hydrogencarbonate solution, water and saturated brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was crystallized from methanol-diethyl ether to give the title compound as a white powder (0.058 g, 71%).

Workup

  1. washwashed successively with 0.05N hydrochloric acid, aqueous sodium hydrogencarbonate solution, water and saturated brine
  2. dry with materialdried over sodium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. customthe residue was crystallized from methanol-diethyl ether

Sources & evidence

ORD record
ord-6a97e04b1c1e46fda93631a6ca2fbde6
Source dataset
uspto-grants-2011_03
Patent number
US07915267B2

Reaction notes

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