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

HRID 2067016Notes

Reaction equation

HRID 2067016 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]([S:26][CH3:27])=[CH:22][C:21]=1[F:28])=[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]([S:26][CH3:27])=[CH:22][C:21]=1[F:28])=[O:9]

Participants

4

Reactant 1

HCID 595652208-(2-Fluoro-4-methylsulfanyl-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amide

Product 1

HCID 441372248-(2-Fluoro-4-methylsulfanyl-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-hydroxy-ethoxy)-amideYield 51.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

8-(2-Fluoro-4-methylsulfanyl-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amide (160 mg, 0.40 mmol) was dissolved in methanol and loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2M NH3 in MeOH. The eluent was collected and concentrated to give a residue, which was subjected to flash chromatography (Si-PPC, gradient 0% to 10%, methanol in dichloromethane) to afford the title compound as a pale yellow solid (77 mg, 51%). LCMS (method A): RT=5.96 min, [M+H]+=377. 1H NMR (DMSO-d6) 11.54 (1 H, s), 10.51 (1 H, s), 8.29 (1 H, d, J=0.80 Hz), 7.80 (1 H, dd, J=7.37, 0.94 Hz), 7.24-7.16 (2 H, m), 7.06 (1 H, dd, J=8.38, 2.11 Hz), 6.80-6.74 (1 H, m), 6.39 (1 H, s), 4.70 (1 H, s), 3.86 (2 H, t, J=4.95 Hz), 3.57 (2 H, t, J=4.95 Hz), 2.49 (3 H, s).

Workup

  1. washThe cartridge was then washed with methanol
  2. washthe desired product was subsequently eluted
  3. customThe eluent was collected
  4. concentrationconcentrated
  5. customto give a residue, which

Sources & evidence

ORD record
ord-66a24320f9c146348fa828b2bc96053f
Source dataset
uspto-grants-2012_10
Patent number
US08293763B2

Reaction notes

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