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

HRID 1428873Notes

Reaction equation

HRID 1428873 reaction equation
[Cl-].[NH4+].O.[CH2:4]([O:6][C:7]([C:9]1[CH:10]=[N:11][N:12]([C:14]2[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:22](=[O:32])[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([N+:33]([O-])=O)[CH:20]=3)[N:15]=2)[CH:13]=1)=[O:8])[CH3:5]>CC(C)=O.[Zn]>[CH2:4]([O:6][C:7]([C:9]1[CH:10]=[N:11][N:12]([C:14]2[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:22](=[O:32])[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([NH2:33])[CH:20]=3)[N:15]=2)[CH:13]=1)=[O:8])[CH3:5]

Participants

6

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 684879631-[6-nitro-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

Product 1

HCID 684879131-[6-amino-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl esterYield 89.5%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 180AcetoneSolvent

Procedure

Ammonium chloride (4.10 g, 76.6 mmol) and water (9.1 mL) were added to a solution of 1-[6-nitro-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (5.92 g, 85% pure, 10.9 mmol) in acetone (46 mL). Zinc dust (5.01 g, 76.6 mmol) was then added in portions with vigorous stirring. Stirring was continued for 45 min, at which point the reaction mixture was filtered through diatomaceous earth. The filter cake was rinsed thoroughly with EtOAc (100 mL). The filtrate was concentrated and the residue was dissolved in EtOAc (75 mL), decanting from the remaining salts. The organic layer was washed with brine (45 mL), dried (MgSO4), and concentrated. The residue was purified by FCC (2-70% EtOAc/hexanes) to yield the titled compound (4.19 g, 89% yield). MS (ESI/Cl): mass calcd. for C20H27N5O4Si, 430.2; m/z found, 429.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.56 (d, J=0.6 Hz, 1H), 8.15 (d, J=0.6 Hz, 1H), 7.53 (d, J=8.6 Hz, 1H), 7.49 (d, J=2.6 Hz, 1H), 7.13 (dd, J=8.6, 2.8 Hz, 1H), 5.78 (s, 2H), 4.35 (q, J=7.1 Hz, 2H), 4.09 (s, 2H), 3.57-3.43 (m, 2H), 1.37 (t, J=7.1 Hz, 3H), 0.86-0.74 (m, 2H), -0.08 (s, 9H).

Workup

  1. filtrationwas filtered through diatomaceous earth
  2. washThe filter cake was rinsed thoroughly with EtOAc (100 mL)
  3. concentrationThe filtrate was concentrated
  4. dissolutionthe residue was dissolved in EtOAc (75 mL)
  5. customdecanting from the remaining salts
  6. washThe organic layer was washed with brine (45 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue was purified by FCC (2-70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-1227b33f2614497f8d1811f368052f35
Source dataset
uspto-grants-2015_01
Patent number
US08937078B2

Reaction notes

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