Potassium Carbonate → HCID 86635032, compound

HRID 908503Notes

Reaction equation

HRID 908503 reaction equation
Cl[C:2]1[N:31]=[CH:30][C:5]2[N:6]=[C:7]3[CH2:12][C@H:11]([C:13]4[CH:18]=[C:17]([F:19])[C:16]([F:20])=[CH:15][C:14]=4[F:21])[C@@H:10]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:9][N:8]3[C:4]=2[CH:3]=1.[CH:32]1(B(O)O)[CH2:34][CH2:33]1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[CH:32]1([C:2]2[N:31]=[CH:30][C:5]3[N:6]=[C:7]4[CH2:12][C@H:11]([C:13]5[CH:18]=[C:17]([F:19])[C:16]([F:20])=[CH:15][C:14]=5[F:21])[C@@H:10]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:27])([CH3:28])[CH3:26])[CH2:9][N:8]4[C:4]=3[CH:3]=2)[CH2:34][CH2:33]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 86635033HCID 86635033, compound

Product 1

HCID 86635032HCID 86635032, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

An oven dried flask charged with 52 mg (0.115 mmol) of tert-butyl [(7R,8R)-3-chloro-8-(2,4,5-trifluorophenyl)-6,7,8,9-tetrahydropyrido[3′,4′:4,5]imidazo[1,2-a]pyridine-7-yl]carbamate (Boc-protected intermediate of Example 5), 12 mg (0.14 mmol) of cyclopropylboronic acid, 64 mg (0.46 mmol) of potassium carbonate, 13 mg (0.0115 mmol) of tetrakis(triphenylphosphine)palladium(0) and 1.5 mL of dry dioxane was put under nitrogen and heated to reflux for 72 h. The reaction mixture was cooled to ambient temperature, filtered through a pad of Celite and the filter cake rinsed with 50 mL of ethyl acetate. The filtrate was evaporated in vacuo and the crude residue was purified directly by reverse phase HPLC(YMC Pro-C18 column, gradient elution, 5% to 90% acetonitrile/water with 0.1% TFA) to afford the title compound as a white foam. LC/MS 459.2 (M+1).

Workup

  1. customAn oven dried flask
  2. temperatureheated
  3. temperatureto reflux for 72 h
  4. filtrationfiltered through a pad of Celite
  5. washthe filter cake rinsed with 50 mL of ethyl acetate
  6. customThe filtrate was evaporated in vacuo
  7. customthe crude residue was purified directly by reverse phase HPLC(YMC Pro-C18 column, gradient elution, 5% to 90% acetonitrile/water with 0.1% TFA)

Sources & evidence

ORD record
ord-d97478a0f2f44e2ba52e0423a3fab9a4
Source dataset
uspto-grants-2011_09
Patent number
US08017624B2

Reaction notes

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