1-Hydroxybenzotriazole → methyl (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butanoate

HRID 736948Notes

Reaction equation

HRID 736948 reaction equation
[NH2:1][C:2]1[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][C:5]([CH2:6][C@@H:7]([CH2:12][C:13]([O-:15])=O)[C:8]([O:10][CH3:11])=[O:9])=[CH:4][C:3]=1[Cl:22].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:64]1[CH2:69][CH2:68][CH:67]([N:70]2[CH2:79][C:78]3[C:73](=[CH:74][CH:75]=[CH:76][CH:77]=3)[NH:72][C:71]2=[O:80])[CH2:66][CH2:65]1>CN(C=O)C>[NH2:1][C:2]1[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][C:5]([CH2:6][C@@H:7]([CH2:12][C:13](=[O:15])[N:64]2[CH2:65][CH2:66][CH:67]([N:70]3[CH2:79][C:78]4[C:73](=[CH:74][CH:75]=[CH:76][CH:77]=4)[NH:72][C:71]3=[O:80])[CH2:68][CH2:69]2)[C:8]([O:10][CH3:11])=[O:9])=[CH:4][C:3]=1[Cl:22]

Participants

7

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 866042951-methyl (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-succinate

Product 1

HCID 68590116methyl (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3.0 g (8.83 mmol) 1-methyl (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-succinate and 3.05 g (9.5 mmol) TBTU, 1.28 g (9.47 mmol) HOBT in 1.7 mL (9.76 mmol) ethyldiisopropylamine and 1100 mL DMF was stirred for 1 h at RT. Then 2.2 g (9.51 mmol) 3-piperidin-4-yl-3,4-dihydro-1H-quinazolin-2-one were added and the reaction solution was stirred overnight at RT. The reaction mixture was evaporated down i.vac., the residue was taken up in DCM, washed with 10% citric acid solution and 15% K2CO3 solution and dried over Na2SO4. The desiccant was eliminated by filtering through activated charcoal; after elimination of the solvent the desired product was obtained.

Workup

  1. customThe reaction mixture was evaporated down i.vac
  2. washwashed with 10% citric acid solution and 15% K2CO3 solution
  3. dry with materialdried over Na2SO4
  4. filtrationby filtering through activated charcoal

Sources & evidence

ORD record
ord-1f8141c844b94560b44713660f3836cc
Source dataset
uspto-grants-2009_09
Patent number
US07595312B2

Reaction notes

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