Triethylamine → 3-(4-Fluorophenyl)-imidazo[1,5-a]pyridine-8-carboxylic acid (2-bromopyridin-4-ylmethyl)-amide

HRID 1423026Notes

Reaction equation

HRID 1423026 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]3[CH:13]=[CH:14][CH:15]=[C:16]([C:17]([OH:19])=O)[C:11]3=[CH:10][N:9]=2)=[CH:4][CH:3]=1.CCN(CC)CC.F[P-](F)(F)(F)(F)F.N1([PH+](N2CCCC2)N2CCCC2)CCCC1.Cl.Cl.[Br:52][C:53]1[CH:58]=[C:57]([CH2:59][NH2:60])[CH:56]=[CH:55][N:54]=1>CN(C=O)C.[Cl-].[NH4+]>[Br:52][C:53]1[CH:58]=[C:57]([CH2:59][NH:60][C:17]([C:16]2[C:11]3[N:12]([C:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)=[N:9][CH:10]=3)[CH:13]=[CH:14][CH:15]=2)=[O:19])[CH:56]=[CH:55][N:54]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 22226026Tripyrrolidinophosphonium hexafluorophosphateHCID 671947383-(4-Fluorophenyl)imidazo[1,5-a]pyridine-8-carboxylic acidHCID 86672832(2-Bromopyridin-4-yl)methanamine dihydrochloride

Product 1

HCID 529356433-(4-Fluorophenyl)-imidazo[1,5-a]pyridine-8-carboxylic acid (2-bromopyridin-4-ylmethyl)-amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a mixture of 3-(4-fluorophenyl)-imidazo[1,5-a]pyridine-8-carboxylic acid (125 mg, 0.488 mmol) and Et3N (0.400 mL, 2.88 mmol) in DMF (3 mL) is added benzotriazol-1-yloxy)tripyrrolidinophosphoniumhexafluorophosphate (PyBOP) (0.300 g, 0.577 mmol). After 10 minutes, C-(2-bromopyridin-4-yl)-methylamine di-hydrochloride salt (153 mg, 0.589 mmol) is added and the mixture is stirred at room temperature. After 2 hours, the mixture is diluted with saturated aqueous ammonium chloride (10 mL) and extracted with EtOAc (3×7 mL). The combined organic layers are washed with saturated aqueous ammonium chloride (2×10 mL), brine (2×10 mL), dried over magnesium sulfate, filtered and concentrated. The residue is purified by silica gel chromatography eluting with a gradient of 0-2% methanol in dichloromethane. The resulting solid is triturated with ethyl ether to afford the title compound.

Workup

  1. waitAfter 2 hours
  2. extractionextracted with EtOAc (3×7 mL)
  3. washThe combined organic layers are washed with saturated aqueous ammonium chloride (2×10 mL), brine (2×10 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel chromatography
  8. washeluting with a gradient of 0-2% methanol in dichloromethane
  9. customThe resulting solid is triturated with ethyl ether

Sources & evidence

ORD record
ord-a10a2e4485e543b5b8fb7bd940711e43
Source dataset
uspto-grants-2015_01
Patent number
US08927550B2

Reaction notes

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