1-Hydroxybenzotriazole → diethyl 2-(3,4-dimethyl-benzyl)-2-{2-oxo-2-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-ethyl}-malonate

HRID 644366Notes

Reaction equation

HRID 644366 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([C:20]([O:22][CH2:23][CH3:24])=[O:21])([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:11][C:12](O)=[O:13])[CH:5]=[CH:6][C:7]=1[CH3:8].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)C(C)C)C.[NH:66]1[CH2:71][CH2:70][CH:69]([N:72]2[CH2:81][C:80]3[C:75](=[CH:76][CH:77]=[CH:78][CH:79]=3)[NH:74][C:73]2=[O:82])[CH2:68][CH2:67]1>O.C1COCC1>[CH3:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[CH3:8])[CH2:9][C:10]([CH2:11][C:12](=[O:13])[N:66]1[CH2:67][CH2:68][CH:69]([N:72]2[CH2:81][C:80]3[C:75](=[CH:76][CH:77]=[CH:78][CH:79]=3)[NH:74][C:73]2=[O:82])[CH2:70][CH2:71]1)([C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:15]([O:17][CH2:18][CH3:19])=[O:16]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 110425973-(Piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-oneHCID 685789934-(3,4-Dimethyl-phenyl)-3,3-bis-ethoxycarbonyl-butanoic acid

Product 1

HCID 68579159diethyl 2-(3,4-dimethyl-benzyl)-2-{2-oxo-2-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-ethyl}-malonate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 10.0 g (29.7 mmol) 4-(3,4-dimethyl-phenyl)-3,3-bis-ethoxycarbonyl-butanoic acid, 10.5 g (32.7 mmol) TBTU, 4.2 g (30.5 mmol) HOBt, 5.8 mL (32.4 mmol) ethyldiisopropylamine, 270 mL THF and 30 mL water was stirred for 15 min at RT and then combined with 7.6 g (32.9 mmol) 3-piperidin-4-yl-3,4-dihydro-1H-quinazolin-2-one. The reaction mixture was stirred for 5 h at RT and evaporated down under reduced pressure. The residue was stirred with 150 mL saturated NaHCO3 solution, suction filtered, washed with water and dried in the circulating air dryer.

Workup

  1. stirringThe reaction mixture was stirred for 5 h at RT
  2. customevaporated down under reduced pressure
  3. stirringThe residue was stirred with 150 mL saturated NaHCO3 solution, suction
  4. filtrationfiltered
  5. washwashed with water
  6. customdried in the circulating air dryer

Sources & evidence

ORD record
ord-85f96a28cc34453486f7c8f4b29cfde3
Source dataset
uspto-grants-2010_04
Patent number
US07700589B2

Reaction notes

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