8-(4-Bromo-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amide → 8-(4-Bromo-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-hydroxy-ethoxy)-amide

HRID 2067024Notes

Reaction equation

HRID 2067024 reaction equation
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:15]=[CH:14][N:13]2[CH:16]=[N:17][CH:18]=[C:12]2[C:11]=1[NH:19][C:20]1[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][C:21]=1[F:27])=[O:9])=C>CO.ClCCl>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:15]=[CH:14][N:13]2[CH:16]=[N:17][CH:18]=[C:12]2[C:11]=1[NH:19][C:20]1[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][C:21]=1[F:27])=[O:9]

Participants

4

Reactant 1

HCID 595652228-(4-Bromo-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amide

Product 1

HCID 441373628-(4-Bromo-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-hydroxy-ethoxy)-amideYield 29.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

8-(4-Bromo-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amide (40 mg, 0.09 mmol) was dissolved in methanol and loaded onto an Isolute® SCX-2 cartridge (5 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2M NH3 in MeOH. Appropriate fractions were combined and concentrated to give a residue that was subjected to flash chromatography (Si-PPC, gradient 0% to 20%, methanol in dichloromethane) to afford the title compound as a pale yellow solid (11 mg, 29%). LCMS (method A): RT=6.06 min, [M+H]+=409/411. 1H NMR (CD3OD): 8.27 (1 H, d, J=0.85 Hz), 7.79 (1 H, dd, J=7.39, 0.97 Hz), 7.42 (1 H, dd, J=10.00, 2.19 Hz), 7.31 (1 H, ddd, J=8.53, 2.20, 1.19 Hz), 7.12 (1 H, t, J=8.60 Hz), 6.79-6.73 (1 H, m), 6.65 (1 H, s), 3.97 (2 H, t, J=4.69 Hz), 3.73 (2 H, t, J=4.68 Hz).

Workup

  1. washThe cartridge was then washed with methanol
  2. washthe desired product was subsequently eluted
  3. concentrationconcentrated
  4. customto give a residue that

Sources & evidence

ORD record
ord-d99cb865cb38479bbb2fd266fcfe7ba1
Source dataset
uspto-grants-2012_10
Patent number
US08293763B2

Reaction notes

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