1-Hydroxybenzotriazole → 4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic Acid {1-(3,4-dimethyl-benzyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 644378Notes

Reaction equation

HRID 644378 reaction equation
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.[CH3:42][C:43]1[CH:44]=[C:45]([CH2:50][CH:51]([NH:55][C:56]([N:58]2[CH2:63][CH2:62][CH:61]([N:64]3[CH2:73][C:72]4[C:67](=[CH:68][CH:69]=[CH:70][CH:71]=4)[NH:66][C:65]3=[O:74])[CH2:60][CH2:59]2)=[O:57])[C:52]([OH:54])=O)[CH:46]=[CH:47][C:48]=1[CH3:49].[CH3:75][N:76]1[CH2:81][CH2:80][N:79]([CH:82]2[CH2:87][CH2:86][NH:85][CH2:84][CH2:83]2)[CH2:78][CH2:77]1>CN(C=O)C.C1COCC1>[CH3:42][C:43]1[CH:44]=[C:45]([CH:46]=[CH:47][C:48]=1[CH3:49])[CH2:50][CH:51]([NH:55][C:56]([N:58]1[CH2:59][CH2:60][CH:61]([N:64]2[CH2:73][C:68]3[C:67](=[CH:72][CH:71]=[CH:70][CH:69]=3)[NH:66][C:65]2=[O:74])[CH2:62][CH2:63]1)=[O:57])[C:52]([N:85]1[CH2:84][CH2:83][CH:82]([N:79]2[CH2:78][CH2:77][N:76]([CH3:75])[CH2:81][CH2:80]2)[CH2:87][CH2:86]1)=[O:54]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7957071-Methyl-4-(piperidin-4-yl)piperazineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 68580202HCID 68580202, compound

Product 1

HCID 592609644-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic Acid {1-(3,4-dimethyl-benzyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl}-amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

0.90 g (2.80 mmol) TBTU, 0.35 g (2.55 mol) HOBt, 0.49 mL (2.80 mmol) ethyldiisopropylamine was added to a mixture of 1.15 g (2.55 mol) 3-(3,4-dimethyl-phenyl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid and 100 mL THF and the mixture was stirred for 30 min at RT. Then 20 mL DMF was added, the mixture was stirred for 15 min and combined with 0.49 g (2.65 mmol) 1-methyl-4-piperidin-4-yl-piperazine. The reaction mixture was stirred overnight at RT, evaporated down under reduced pressure and the residue was combined with 70 mL saturated NaHCO3 solution. The aqueous phase was extracted three times with DCM, the combined organic phases were dried over Na2SO4, filtered and evaporated down under reduced pressure. The residue was purified by column chromatography over silica gel, the product fractions were evaporated down under reduced pressure, triturated with diethyl ether and suction filtered.

Workup

  1. stirringthe mixture was stirred for 15 min
  2. stirringThe reaction mixture was stirred overnight at RT
  3. customevaporated down under reduced pressure
  4. extractionThe aqueous phase was extracted three times with DCM
  5. dry with materialthe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated down under reduced pressure
  8. customThe residue was purified by column chromatography over silica gel
  9. customthe product fractions were evaporated down under reduced pressure
  10. customtriturated with diethyl ether and suction
  11. filtrationfiltered

Sources & evidence

ORD record
ord-185dfd7aebfc469683129e17db241a3e
Source dataset
uspto-grants-2010_04
Patent number
US07700589B2

Reaction notes

Loading…