5-bromo-7-methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole → (6-chloro-pyrimidin-4-yl)-[7-methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazol-5-yl]-methanone

HRID 469306Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH3:11])[CH:10]=1)[N:7]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[N:6]=[CH:5]2.C([Li])CCC.CON(C)[C:28]([C:30]1[CH:35]=[C:34]([Cl:36])[N:33]=[CH:32][N:31]=1)=[O:29]>C1COCC1>[Cl:36][C:34]1[N:33]=[CH:32][N:31]=[C:30]([C:28]([C:2]2[CH:3]=[C:4]3[C:8](=[C:9]([CH3:11])[CH:10]=2)[N:7]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[N:6]=[CH:5]3)=[O:29])[CH:35]=1

Participants

Conditions

Temperature: -75 °C

Procedure

Under an argon atmosphere 0.34 g (1.00 mmol) 5-bromo-7-methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole in 10 mL THF were cooled to −75° C., mixed with 0.70 mL (1.1 mmol) of a 1.6 molar n-butyllithium solution and stirred for 1 h at −75° C. Then 0.25 g (1.1 mmol) 6-chloro-pyrimidine-4-carboxylic acidmethoxy-methyl-amide, dissolved in a little THF, were added dropwise. The cooling bath was removed and the mixture was heated to 0° C. and stirred for a further hour in the ice bath. The mixture was stirred with saturated sodium hydrogen carbonate solution, extracted with EtOAc, the organic phase was dried and evaporated down. The residue was purified by flash chromatography.

Workup

additionwere added dropwise
customThe cooling bath was removed
temperaturethe mixture was heated to 0° C.
stirringstirred for a further hour in the ice bath
stirringThe mixture was stirred with saturated sodium hydrogen carbonate solution
extractionextracted with EtOAc
customthe organic phase was dried
customevaporated down
customThe residue was purified by flash chromatography

Sources & evidence

ORD record: ord-79699a7416d048da97bd66966e2eff2c
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08629137B2

Reaction notes

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