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

HRID 1428843Notes

Reaction equation

HRID 1428843 reaction equation
CCN(C(C)C)C(C)C.[CH2:10]([O:12][C:13]([C:15]1[CH:16]=[N:17][N:18]([C:20]2[NH:29][C:28](=[O:30])[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([Br:31])[CH:26]=3)[N:21]=2)[CH:19]=1)=[O:14])[CH3:11].Cl[CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38]>C1COCC1>[CH2:10]([O:12][C:13]([C:15]1[CH:16]=[N:17][N:18]([C:20]2[N:29]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[C:28](=[O:30])[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([Br:31])[CH:26]=3)[N:21]=2)[CH:19]=1)=[O:14])[CH3:11]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 1363371691-(6-bromo-4-oxo-3,4-dihydro-quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester

Product 1

HCID 684885541-[6-bromo-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl esterYield 95.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

DIEA (1.23 mL, 7.08 mmol) was added to 1-(6-bromo-4-oxo-3,4-dihydro-quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester (0.980 g, 2.70 mmol) in THF (13.5 mL), followed by (2-chloromethoxy-ethyl)-trimethyl-silane (0.500 mL, 3.27 mmol). The reaction mixture was stirred at room temperature for 18 h, and concentrated. The residue was purified by FCC (0-20% EtOAc/hexanes) to yield the titled compound (1.27 g, 95% yield). MS (ESI/Cl): mass calcd. for C20H25BrN4O4Si, 492.1; m/z found, 435.1 [M−58+H]+.

Workup

  1. concentrationconcentrated
  2. customThe residue was purified by FCC (0-20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-0f7472905d024b10ab0f5158f6378c9b
Source dataset
uspto-grants-2015_01
Patent number
US08937078B2

Reaction notes

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