Phosgene → N-{1-benzyl-3-[4-(benzyloxy)benzyl]-2-oxoazepan-3-yl}-4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidine-1-carboxamide

HRID 1271501Notes

Reaction equation

HRID 1271501 reaction equation
[C:1](Cl)(Cl)=[O:2].[NH2:5][C:6]1([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[CH:24][CH:23]=2)[CH2:12][CH2:11][CH2:10][CH2:9][N:8]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:7]1=[O:20].C(N(CC)CC)C.C(N(C(C)C)CC)(C)C.[Cl-].[O:53]=[C:54]1[N:63]([CH:64]2[CH2:69][CH2:68][NH2+:67][CH2:66][CH2:65]2)[CH2:62][C:61]2[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=2)[NH:55]1>ClCCl>[CH2:13]([N:8]1[CH2:9][CH2:10][CH2:11][CH2:12][C:6]([NH:5][C:1]([N:67]2[CH2:68][CH2:69][CH:64]([N:63]3[CH2:62][C:61]4[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=4)[NH:55][C:54]3=[O:53])[CH2:65][CH2:66]2)=[O:2])([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([O:28][CH2:29][C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)=[CH:26][CH:27]=2)[C:7]1=[O:20])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

7

Reactant 5

HCID 6371PhosgeneHCID 8471TriethylamineHCID 81531DiisopropylethylamineHCID 184519093-Amino-1-benzyl-3-[4-(benzyloxy)benzyl]azepan-2-oneHCID 178517128HCID 178517128, compound

Product 1

HCID 18451933N-{1-benzyl-3-[4-(benzyloxy)benzyl]-2-oxoazepan-3-yl}-4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidine-1-carboxamideYield 94.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Phosgene (20% wt. in toluene; 0.49 mL, 0.92 mmol) was added to a solution of 3-amino-1-benzyl-3-[4-(benzyloxy)benzyl]azepan-2-one (76 mg, 0.18 mmol) and triethylamine (0.80 mL, 0.55 mmol) in dichloromethane (2 mL) at 0° C. After 30 min, the mixture was concentrated and redissoved in acetonitrile (5 mL). Diisopropylethylamine (0.060 mL, 0.37 mmol), and 4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidinium chloride (49 mg, 0.18 mmol) were added and the mixture was heated to reflux. After 1 h, the mixture was allowed to cool to ambient temperature and concentrated. Purification by silica gel chromatography (1% methanol/dichloromethane→5% methanol/dichloromethane gave the title compound (114 mg). MS 672 (M+1).

Workup

  1. concentrationthe mixture was concentrated
  2. temperaturethe mixture was heated to reflux
  3. waitAfter 1 h
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography (1% methanol/dichloromethane→5% methanol/dichloromethane

Sources & evidence

ORD record
ord-b51f4baebc884feb8751bbe7527f9d58
Source dataset
uspto-grants-2007_04
Patent number
US07205292B2

Reaction notes

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