Methanamine, N-methoxy-, hydrochloride (1:1) → 8-chloro-5-(3-fluorophenyl)-N-methoxy-N-methylimidazo[1,5-a]pyridine-6-carboxamide

HRID 717821Notes

Reaction equation

HRID 717821 reaction equation
[Cl:1][C:2]1[C:3]2[N:4]([CH:18]=[N:19][CH:20]=2)[C:5]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[C:6]([C:8]([OH:10])=O)[CH:7]=1.C(N(CC)C(C)C)(C)C.Cl.[CH3:31][NH:32][O:33][CH3:34].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(=O)(O)[O-].[Na+]>CN(C)C=O>[Cl:1][C:2]1[C:3]2[N:4]([CH:18]=[N:19][CH:20]=2)[C:5]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[C:6]([C:8]([N:32]([O:33][CH3:34])[CH3:31])=[O:10])[CH:7]=1

Participants

8

Reactant 6

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 585159988-Chloro-5-(3-fluorophenyl)imidazo[1,5-a]pyridine-6-carboxylic acid

Product 1

HCID 585159348-chloro-5-(3-fluorophenyl)-N-methoxy-N-methylimidazo[1,5-a]pyridine-6-carboxamideYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

8-Chloro-5-(3-fluorophenyl)imidazo[1,5-a]pyridine-6-carboxylic acid (0.29 g, 1.0 mmol) was stirred in N,N-dimethylformamide (2.8 mL). N,N-Diisopropylethylamine (0.87 mL, 5.0 mmol), N,O-dimethylhydroxylamine hydrochloride (0.29 g, 3.0 mmol) and a solution of 0.6 N 1-hydroxy-7-azabenzotriazole in N,N-dimethylformamide (0.33 mL, 0.2 mmol) were added. The mixture was stirred for 5 minutes and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.29 g, 1.5 mmol) was added. The mixture was stirred for 2 hours. The mixture was poured into saturated sodium bicarbonate and extracted into ethyl acetate 3×. The ethyl acetate extracts were combined and washed with water, dried over sodium sulfate, filtered, concentrated and purified by flash column chromatography with ethyl acetate in hexanes (0-80%) to give the desired compound (0.20 g, 60%). LCMS calculated for C16H14ClFN3O2 (M+H)+: m/z=334.1. found: 333.9. 1H NMR (300 MHz, DMSO-d6): δ 8.10 (s, 1H), 7.60 (m, 2H), 7.42 (m, 3H), 7.20 (s, 1H), 3.41 (br s, 3H), 3.00 (s, 3H).

Workup

  1. stirringThe mixture was stirred for 2 hours
  2. extractionextracted into ethyl acetate 3×
  3. washwashed with water
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by flash column chromatography with ethyl acetate in hexanes (0-80%)

Sources & evidence

ORD record
ord-9b1f5653409040d490e3b4fd541ad71c
Source dataset
uspto-grants-2015_11
Patent number
US09193721B2

Reaction notes

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