Benzaldehyde → 1-[6-benzylamino-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1428879Notes

Reaction equation

HRID 1428879 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:19](=[O:29])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([NH2:30])[CH:17]=3)[N:12]=2)[CH:10]=1)=[O:5])[CH3:2].[CH:31](=O)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:19](=[O:29])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([NH:30][CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:17]=3)[N:12]=2)[CH:10]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 240BenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 684879131-[6-amino-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

Product 1

HCID 684886321-[6-benzylamino-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl esterYield 90.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A vial was charged with 1-[6-amino-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (0.250 g, 0.582 mmol), benzaldehyde (59.2 μL, 0.582 mmol), and 4 Å MS (0.25 g). DCE was added (1.9 mL) and the reaction mixture was stirred at room temperature for 18 h. Sodium triacetoxyborohydride (0.308 g, 1.46 mmol) was added and the reaction mixture was stirred for a further 24 h. The reaction was quenched with saturated aqueous sodium bicarbonate (10 mL) and was then extracted with DCM (3×15 mL). The combined organic layers were washed with brine (20 mL), dried (MgSO4), and concentrated. The residue was purified by FCC (2-40% EtOAc/hexanes) to yield the titled compound (0.273 g, 90% yield). MS (ESI/Cl): mass calcd. for C27H33N5O4Si, 519.2; m/z found, 520.2 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred for a further 24 h
  2. customThe reaction was quenched with saturated aqueous sodium bicarbonate (10 mL)
  3. extractionwas then extracted with DCM (3×15 mL)
  4. washThe combined organic layers were washed with brine (20 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue was purified by FCC (2-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-fe063256a10944cebc210734386fab2e
Source dataset
uspto-grants-2015_01
Patent number
US08937078B2

Reaction notes

Loading…