Sodium Carbonate → HCID 25120173, compound

HRID 1893474Notes

Reaction equation

HRID 1893474 reaction equation
Br[C:2]1[N:6]2[C:7]3[C:12]([N:13]=[C:14]([NH:15][CH2:16][CH2:17][CH2:18][OH:19])[C:5]2=[N:4][CH:3]=1)=[CH:11][C:10]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:9][CH:8]=3.[NH:25]1[CH:29]=[CH:28][C:27](B(O)O)=[N:26]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C(OCC)(=O)C.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>[N:25]1[NH:26][C:27]([C:2]2[N:6]3[C:7]4[C:12]([N:13]=[C:14]([NH:15][CH2:16][CH2:17][CH2:18][OH:19])[C:5]3=[N:4][CH:3]=2)=[CH:11][C:10]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:9][CH:8]=4)=[CH:28][CH:29]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 59333306HCID 59333306, compoundHCID 178514837HCID 178514837, compound

Product 1

HCID 25120173HCID 25120173, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 3-(1-bromo-7-trifluoromethoxy-imidazo[1,2-a]quinoxalin-4-ylamino)-propan-1-ol (300 mg; 0.74 mmol; 1 eq) in N,N-dimethylformamide (8 mL), pyrazoleboronic acid (166 mg, 1.48 mmol; 2 eq) is added under argon followed by sodium carbonate (314 mg; 2.96 mmol; 4 eq) and tetrakis(triphenylphosphine)palladium (257 mg; 0.22 mmol; 0.3 eq). The solution is allowed to stir for 17 hours at 130° C. until the reaction is complete on TLC. The crude mixture is cooled to room temperature, diluted with ethyl acetate (50 mL), washed once with a saturated solution of sodium hydrogenocarbonate (90 mL) and three times with brine (3×25 mL). The resulting organic phase is dried over sodium sulfate, filtered and concentrated under vacuum to afford a crude brown powder. This solid is purified by chromatography on silica gel (gradient dichloromethane/methanol 98:2→95:5) to afford the title compound as an orange powder. Recristallization of this solid from ethyl acetate at 0-5° C. afforded the pure title compound (88 mg; 0.22 mmol; 30%) after filtration, washing with diethyl ether and drying of the resulting beige powder.

Workup

  1. washwashed once with a saturated solution of sodium hydrogenocarbonate (90 mL) and three times with brine (3×25 mL)
  2. dry with materialThe resulting organic phase is dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customto afford a crude brown powder
  6. customThis solid is purified by chromatography on silica gel (gradient dichloromethane/methanol 98:2→95:5)

Sources & evidence

ORD record
ord-1ac2c63bd61540f4b648faf424514766
Source dataset
uspto-grants-2013_08
Patent number
US08513250B2

Reaction notes

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