Potassium Carbonate → HCID 178504756, compound

HRID 869280Notes

Reaction equation

HRID 869280 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]([NH2:10])=[O:9])[C:5]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([S:18]([CH3:21])(=[O:20])=[O:19])[CH:13]=2)=[N:4][C:3]=1[NH:22][C@H:23]1[CH2:28][CH2:27][C@H:26]([OH:29])[CH2:25][CH2:24]1.[CH:30]1(B(O)O)[CH2:32][CH2:31]1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>O>[CH:30]1([C:2]2[N:7]=[C:6]([C:8]([NH2:10])=[O:9])[C:5]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([S:18]([CH3:21])(=[O:20])=[O:19])[CH:13]=3)=[N:4][C:3]=2[NH:22][C@H:23]2[CH2:28][CH2:27][C@H:26]([OH:29])[CH2:25][CH2:24]2)[CH2:32][CH2:31]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 2760897Cyclopropylboronic acidHCID 178504755HCID 178504755, compound

Product 1

HCID 178504756HCID 178504756, compoundYield 21.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of 6-bromo-5-[(trans-4-hydroxycyclohexyl)amino]-3-{[3-(methylsulfonyl)phenyl]amino}pyrazine-2-carboxamide (Example 181) (50 mg), cyclopropylboronic acid (18 mg), tetrakistriphenylphosphine palladium (24 mg), potassium carbonate (71 mg), dioxane (2.5 mL) and water (0.5 mL) was stirred at 115° C. overnight. After cooling, the reaction liquid was partitioned using chloroform, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride. After drying, the organic layer was concentrated, and the resulting residue was purified by silica gel column chromatography (eluent; chloroform:methanol:saturated aqueous ammonia=100:0:0 to 10:1:0.1). The resulting residue was solidified with ethyl acetate-hexane to give 6-cyclopropyl-5-[(trans-4-hydroxycyclohexyl)amino]-3-{[3-(methylsulfonyl)phenyl]amino}pyrazine-2-carboxamide (10 mg) as a yellow solid.

Workup

  1. temperatureAfter cooling
  2. customthe reaction liquid
  3. customwas partitioned
  4. customAfter drying
  5. concentrationthe organic layer was concentrated
  6. customthe resulting residue was purified by silica gel column chromatography (eluent; chloroform:methanol:saturated aqueous ammonia=100:0:0 to 10:1:0.1)

Sources & evidence

ORD record
ord-c02b3f0f48f043988fb6ae8f5344da42
Source dataset
uspto-grants-2015_03
Patent number
US08969336B2

Reaction notes

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