Hydrochloric Acid → 7-acetyl-N-(1-benzyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 706737Notes

Reaction equation

HRID 706737 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[C:12]([NH:17][C:18]([C:20]3[N:24]4[CH:25]=[CH:26][C:27](Br)=[CH:28][C:23]4=[N:22][CH:21]=3)=[O:19])[CH:13]=[CH:14][CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C([Sn](CCCC)(CCCC)[C:57]([O:59]CC)=[CH2:58])CCC.C(N(CC)CC)C.Cl>CO.C(Cl)Cl.CN(C=O)C>[C:57]([C:27]1[CH:26]=[CH:25][N:24]2[C:20]([C:18]([NH:17][C:12]3[CH:13]=[CH:14][CH:15]=[C:16]4[C:11]=3[CH:10]=[N:9][N:8]4[CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:19])=[CH:21][N:22]=[C:23]2[CH:28]=1)(=[O:59])[CH3:58]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 67976233N-(1-benzyl-1H-indazol-4-yl)-7-bromoimidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 679759587-acetyl-N-(1-benzyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 39.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
100 °C

Procedure

A dried flask flushed with nitrogen was charged with N-(1-benzyl-1H-indazol-4-yl)-7-bromoimidazo[1,2-a]pyridine-3-carboxamide (150 mg, 0.34 mmol), tri-o-tolylphosphine (20 mg, 0.067 mmol), tris-dibenzylideneacetone dipalladium (0) (31 mg, 0.033 mmol), anhydrous DMF (4.5 mL) and tributyl(1-ethoxyvinyl)stannane (0.13 mL, 0.39 mmol). The resulting mixture was immediately degassed under a nitrogen atmosphere, triethylamine (0.056 mL, 0.40 mmol) was added, and the flask was heated at 100° C. for 6 hours. To the cooled reaction was added concentrated aqueous hydrochloric acid (0.5 mL) and stirring was continued at ambient temperature for two hours. The reaction was quenched with excess saturated aqueous sodium bicarbonate, and the resulting suspension was extracted with EtOAc and DCM. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated to afford the crude product. The crude product was subjected to preparative thin-layer chromatography on silica with 4% MeOH/DCM as eluent to afford 55 mg of desired product as an off-white solid. MS (ES+APCI) m/z=410 (M+H) detected.

Workup

  1. customA dried flask flushed with nitrogen
  2. customThe resulting mixture was immediately degassed under a nitrogen atmosphere
  3. customTo the cooled reaction
  4. customThe reaction was quenched with excess saturated aqueous sodium bicarbonate
  5. extractionthe resulting suspension was extracted with EtOAc and DCM
  6. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customto afford the crude product

Sources & evidence

ORD record
ord-136a314447a1481781192ff7ce45bbf1
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

Loading…