1-Hydroxybenzotriazole → HCID 69804678, compound

HRID 488418Notes

Reaction equation

HRID 488418 reaction equation
ON1C2C=CC=CC=2N=N1.[Br:11][C:12]1[CH:13]=[C:14]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[C:26]([NH:29][C:30]([CH:32]=[CH:33][C:34](O)=[O:35])=[O:31])[CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH:15]=[CH:16][CH:17]=1.CCN(C(C)C)C(C)C.[CH2:46]([O:48][C:49]([CH2:51][N:52]([CH2:54][CH2:55][CH2:56][NH2:57])[CH3:53])=[O:50])[CH3:47]>CN(C)C=O.O>[Br:11][C:12]1[CH:13]=[C:14]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[C:26]([NH:29][C:30](=[O:31])[CH:32]=[CH:33][C:34]([NH:57][CH2:56][CH2:55][CH2:54][N:52]([CH2:51][C:49]([O:48][CH2:46][CH3:47])=[O:50])[CH3:53])=[O:35])[CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH:15]=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 22269990HCID 22269990, compoundHCID 53786874HCID 53786874, compound

Product 1

HCID 69804678HCID 69804678, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

106 mg of benzotriazol-1-yl-N-tetramethyl-uronium-tetrafluoroborate and 68 mg of 1-hydroxybenzotriazole are added to a solution of 200 mg of 4-[(3-bromophenyl)amino]-6-{[(2-carboxyvinyl)carbonyl]amino}-quinazoline in 2.5 ml of dimethyl-formamide. The solution is stirred for 20 minutes at ambient temperature, then 0.5 ml of Hünig's base and 148 mg of 3-{N-[(ethoxycarbonyl)methyl]-N-methylamino}propylamine, dissolved in 0.5 ml of dimethylformamide, are added. The reaction mixture is stirred for a further two hours at ambient temperature before being poured onto 50 ml of water for working king up. The aqueous phase is extracted with ethyl acetate, the combined organic phases are washed with saturated sodium chloride solution, dried over magnesium sulphate and concentrated by evaporation. The crude product is purified by chromatography on a silica gel column with methylene chloride/ethanol (20:1 to 9:1). Yield: 106 mg (39% of theory), Melting point: 278-279° C. Mass spectrum (ESI*): m/z=569, 571 [M+H]*

Workup

  1. additionare added
  2. stirringThe reaction mixture is stirred for a further two hours at ambient temperature
  3. extractionThe aqueous phase is extracted with ethyl acetate
  4. washthe combined organic phases are washed with saturated sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated by evaporation
  7. customThe crude product is purified by chromatography on a silica gel column with methylene chloride/ethanol (20:1 to 9:1)

Sources & evidence

ORD record
ord-fb43b63a57ed4506899e18d4f0246883
Source dataset
uspto-grants-2005_12
Patent number
US06972288B1

Reaction notes

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