Hydrochloric Acid → 5-(4-Cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-hydroxy-ethoxy)-amide

HRID 2076217Notes

Reaction equation

HRID 2076217 reaction equation
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:11]=[CH:12][C:13]2[N:14]([CH:27]=[N:28][CH:29]=2)[C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]2[CH2:25][CH2:24]2)=[CH:19][C:18]=1[F:26])=[O:9])=C.Cl>CO>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:11]=[CH:12][C:13]2[N:14]([CH:27]=[N:28][CH:29]=2)[C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]2[CH2:24][CH2:25]2)=[CH:19][C:18]=1[F:26])=[O:9]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 591401465-(4-Cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-vinyloxy-ethoxy)-amide

Product 1

HCID 441359805-(4-Cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-hydroxy-ethoxy)-amideYield 41%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 5-(4-cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-vinyloxy-ethoxy)-amide (270 mg, 0.681 mmol) in methanol (10 mL) was added 1M hydrochloric acid (2 mL, 2 mmol.) and the mixture stirred at room temperature for 2 hours. Solvent was removed in vacuo, and then saturated aqueous NaHCO3 added and the mixture extracted with ethyl acetate. The organic layer was separated, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was triturated with TBME and the solid collected by filtration to give the title compound as an off-white solid (103 mg, 41%). LCMS (Method A): RT5.68 [M+H] 371. 1HNMR (DMSO-d6, 400 MHz) 7.81 (1H, s), 7.37-7.34 (1H, m), 7.27 (1H, d, J=9.37 Hz), 6.95 (1H, d, J=9.34 Hz), 6.91 (1H, dd, J=12.49, 1.92 Hz), 6.75 (1H, dd, J=8.27, 1.96 Hz), 6.56-6.46 (1H, m), 3.71-3.65 (2H, m), 3.48-3.43 (2H, m), 1.89-1.80 (1H, m), 0.91-0.85 (2H, m), 0.65-0.57 (2H, m).

Workup

  1. customSolvent was removed in vacuo
  2. additionsaturated aqueous NaHCO3 added
  3. extractionthe mixture extracted with ethyl acetate
  4. customThe organic layer was separated
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resultant residue was triturated with TBME
  9. filtrationthe solid collected by filtration

Sources & evidence

ORD record
ord-09af48555294473b89ed2821032645fd
Source dataset
uspto-grants-2011_04
Patent number
US07923456B2

Reaction notes

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