1-Hydroxybenzotriazole → 1-[1,4']bipiperidinyl-1'-yl-2-(3,4-dimethyl-benzyl)-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butan-1,4-dione

HRID 644368Notes

Reaction equation

HRID 644368 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][C:32]=1[CH3:33])[CH2:5][CH:6]([CH2:10][C:11](=[O:29])[N:12]1[CH2:17][CH2:16][CH:15]([N:18]2[CH2:27][C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[NH:20][C:19]2=[O:28])[CH2:14][CH2:13]1)[C:7](O)=[O: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.[N:75]1([CH:81]2[CH2:86][CH2:85][NH:84][CH2:83][CH2:82]2)[CH2:80][CH2:79][CH2:78][CH2:77][CH2:76]1>O.C1COCC1>[N:75]1([CH:81]2[CH2:86][CH2:85][N:84]([C:7](=[O:8])[CH:6]([CH2:5][C:4]3[CH:30]=[CH:31][C:32]([CH3:33])=[C:2]([CH3:1])[CH:3]=3)[CH2:10][C:11]([N:12]3[CH2:17][CH2:16][CH:15]([N:18]4[CH2:27][C:26]5[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=5)[NH:20][C:19]4=[O:28])[CH2:14][CH2:13]3)=[O:29])[CH2:83][CH2:82]2)[CH2:80][CH2:79][CH2:78][CH2:77][CH2:76]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 786071,4'-BipiperidineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 685810572-(3,4-dimethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butanoic acid

Product 1

HCID 592609951-[1,4']bipiperidinyl-1'-yl-2-(3,4-dimethyl-benzyl)-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butan-1,4-dione

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 0.9 g (2.0 mmol) 2-(3,4-dimethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butanoic acid, 0.71 g (2.2 mmol) TBTU, 0.28 g (2.1 mmol) HOBt, 0.39 mL (2.2 mmol) ethyldiisopropylamine, 45 mL THF and 5 mL water was stirred for 10 min at RT, combined with 0.37 g (2.1 mmol) [1,4′]bipiperidinyl and stirred for a further 4 h. The reaction mixture was evaporated down under reduced pressure, the residue was combined with saturated NaHCO3 solution and extracted three times with DCM/MeOH (95:5). The combined organic phases were dried, evaporated down under reduced pressure and purified by chromatography over silica gel. The product fractions were evaporated down under reduced pressure, the residue was triturated with diisopropylether and suction filtered.

Workup

  1. stirringstirred for a further 4 h
  2. customThe reaction mixture was evaporated down under reduced pressure
  3. extractionextracted three times with DCM/MeOH (95:5)
  4. customThe combined organic phases were dried
  5. customevaporated down under reduced pressure
  6. custompurified by chromatography over silica gel
  7. customThe product fractions were evaporated down under reduced pressure
  8. customthe residue was triturated with diisopropylether and suction
  9. filtrationfiltered

Sources & evidence

ORD record
ord-64d739f75bad45bca4d6b06307557e25
Source dataset
uspto-grants-2010_04
Patent number
US07700589B2

Reaction notes

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