Potassium Carbonate → HCID 57594300, compound

HRID 1714571Notes

Reaction equation

HRID 1714571 reaction equation
Br[C:2]1[C:3]2[N:4]([CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([CH2:17][C@H:18]([NH:22][C:23](=[O:36])[C:24]4[CH:29]=[CH:28][C:27]([O:30][CH:31]([CH3:33])[CH3:32])=[C:26]([C:34]#[N:35])[CH:25]=4)[CH2:19][CH2:20][OH:21])=[CH:13][CH:12]=3)[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:37][C:38]1[C:42](B(O)O)=[C:41]([CH3:46])[O:40][N:39]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:34]([C:26]1[CH:25]=[C:24]([CH:29]=[CH:28][C:27]=1[O:30][CH:31]([CH3:32])[CH3:33])[C:23]([NH:22][C@@H:18]([CH2:17][C:14]1[CH:15]=[CH:16][C:11]([C:9]2[N:10]=[C:3]3[C:2]([C:42]4[C:38]([CH3:37])=[N:39][O:40][C:41]=4[CH3:46])=[CH:7][CH:6]=[CH:5][N:4]3[CH:8]=2)=[CH:12][CH:13]=1)[CH2:19][CH2:20][OH:21])=[O:36])#[N:35]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27343463,5-Dimethylisoxazole-4-boronic acidHCID 11699582HCID 11699582, compound

Product 1

HCID 57594300HCID 57594300, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of N-((1S)-1-{[4-(8-bromoimidazo[1,2-a]pyridin-2-yl)phenyl]methyl}-3-hydroxypropyl)-3-cyano-4-[(1-methylethyl)oxy]benzamide (200 mg, 0.366 mmol) in dry DMF (2 mL) were added 3,5-dimethyl-isoxazole-4-boronic acid (63 mg, 0.439 mmol), tetrakistriphenylphosphine palladium(0) (21 mg, 0.018 mmol) and 2.0M aqueous K2CO3 (0.46 mL) successively at rt. The reaction mixture was purged with argon and heated to 100° C., stirred for 22 h, cooled to rt, filtered and purified directly by reverse phase HPLC (MeCN/H2O with 0.1% TFA). The clean fractions were adjusted to pH ˜8 with saturated aqueous NaHCO3 and extracted with 3% MeOH/EtOAc (3×30 mL). The extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to give 45 mg (22%) of the title compound as an off-white solid. LC/MS (ES) m/e 564.2 (M+H)+.

Workup

  1. customThe reaction mixture was purged with argon
  2. temperaturecooled to rt
  3. filtrationfiltered
  4. custompurified directly by reverse phase HPLC (MeCN/H2O with 0.1% TFA)
  5. extractionextracted with 3% MeOH/EtOAc (3×30 mL)
  6. dry with materialThe extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-92f38c1f2fd242008f8bd81f33bc4ab0
Source dataset
uspto-grants-2010_09
Patent number
US07795448B2

Reaction notes

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