Potassium Carbonate → 1-[6-cyclopropyl-4-oxo-3-(2-trimethylsilanylethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1428844Notes

Reaction equation

HRID 1428844 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](Br)[CH:17]=3)[N:12]=2)[CH:10]=1)=[O:5])[CH3:2].[CH:31]1(B(O)O)[CH2:33][CH2:32]1.C([O-])([O-])=O.[K+].[K+]>[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.Cl[Pd]Cl.[Fe+2].C1COCC1>[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]([CH:31]4[CH2:33][CH2:32]4)[CH:17]=3)[N:12]=2)[CH:10]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 684885541-[6-bromo-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

Product 1

HCID 684868721-[6-cyclopropyl-4-oxo-3-(2-trimethylsilanylethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl esterYield 26.1%

Reagents, catalysts & solvents 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-[6-bromo-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (0.500 g, 1.01 mmol), cyclopropylboronic acid (0.199 g, 2.32 mmol), dichloro(1,1′-bis(diphenylphosphino)ferrocene)palladium(II)dichloromethane adduct (0.100 g, 0.123 mmol), K2CO3 (0.420 g, 3.04 mmol) and THF (10 mL) were purged for 15 minutes with nitrogen and then heated to 80° C. for 15 h. The mixture was cooled to room temperature and filtered through a pad of CELITE®. The filtrate cake was washed with dichloromethane and concentrated. The residue was purified by FCC (0-20% EtOAc/hexanes) to yield the titled compound (0.120 g, 26% yield). MS (ESI/Cl): mass calcd. for C23H30N4O4Si, 454.2; m/z found, 455.2 [M+H]+.

Workup

  1. customwere purged for 15 minutes with nitrogen
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationfiltered through a pad of CELITE®
  4. washThe filtrate cake was washed with dichloromethane
  5. concentrationconcentrated
  6. customThe residue was purified by FCC (0-20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-c02a841d37c440aea8bc450ac28c5840
Source dataset
uspto-grants-2015_01
Patent number
US08937078B2

Reaction notes

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