Sodium Carbonate → 6-(2,4-Dichloro-phenyl)-3-(2-fluoro-pyridin-4-yl)-8-isobutoxy-imidazo[1,2-a]pyridine-7-carbonitrile

HRID 420540Notes

Reaction equation

HRID 420540 reaction equation
Br[C:2]1[N:6]2[CH:7]=[C:8]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=3[Cl:25])[C:9]([C:16]#[N:17])=[C:10]([O:11][CH2:12][CH:13]([CH3:15])[CH3:14])[C:5]2=[N:4][CH:3]=1.[F:26][C:27]1[CH:32]=[C:31](B(O)O)[CH:30]=[CH:29][N:28]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:25][C:19]1[CH:20]=[C:21]([Cl:24])[CH:22]=[CH:23][C:18]=1[C:8]1[C:9]([C:16]#[N:17])=[C:10]([O:11][CH2:12][CH:13]([CH3:15])[CH3:14])[C:5]2[N:6]([C:2]([C:31]3[CH:30]=[CH:29][N:28]=[C:27]([F:26])[CH:32]=3)=[CH:3][N:4]=2)[CH:7]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27833962-Fluoropyridine-4-boronic acidHCID 66659202HCID 66659202, compound

Product 1

HCID 666589656-(2,4-Dichloro-phenyl)-3-(2-fluoro-pyridin-4-yl)-8-isobutoxy-imidazo[1,2-a]pyridine-7-carbonitrileYield 41%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

In a sealed tube, a mixture of 3-bromo-6-(2,4-dichloro-phenyl)-8-isobutoxy-imidazo[1,2-a]pyridine-7-carbonitrile (115 mg, 0.25 mmol, prepared according to Example 35, Step 20.2), 2-fluoro-4-pyridine-boronic acid (45.3 mg, 0.32 mmol), PdCl2(PPh3)2 (9.6 mg, 0.014 mmol) and Na2CO3 (2.0 M solution in water, 0.43 mL) in DME (1 mL) was heated at 150° C. for 25 min in a microwave oven. The reaction mixture was cooled to RT, diluted in AcOEt (20 mL) and washed with water (2×10 mL). The organic layer was dried over Na2SO4, filtered, and evaporated to dryness. The remaining residue was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, hexane/TBME 95:5→6:4) to yield the title compound (46.6 mg, 0.10 mmol, 41%) as a white solid. MS: 455 [M+1]+; HPLC: AtRet=3.18; TLC: RF 0.25 (hexane/TBME 1:1).

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. washwashed with water (2×10 mL)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe remaining residue was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, hexane/TBME 95:5→6:4)

Sources & evidence

ORD record
ord-e8348454385e43a9b80b83fc88504082
Source dataset
uspto-grants-2012_01
Patent number
US08097617B2

Reaction notes

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