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

HRID 2067028Notes

Reaction equation

HRID 2067028 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[Cl:27])=[O:9])=C.C(O)=O.C(#N)C>CO.ClCCl.O>[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[Cl:27])=[O:9]

Participants

7

Reactant 3

HCID 284Formic AcidHCID 6342AcetonitrileHCID 595652238-(4-Bromo-2-chloro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amide

Product 1

HCID 441373648-(4-Bromo-2-chloro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-hydroxy-ethoxy)-amideYield 23.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

8-(4-Bromo-2-chloro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amide (196 mg, 0.43 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. Appropriate fractions were combined and concentrated to give a residue that was subjected to flash chromatography (Si-PPC, gradient 0% to 10%, methanol in dichloromethane). The appropriate fractions were combined and concentrated to give a residue that was subjected to HPLC (Preparative C18 column, 0.1% formic acid, acetonitrile in water, gradient 5% to 98%, ramp time 20 minutes) to afford the title compound as a pale yellow solid (43 mg, 23%). LCMS (method A): RT=6.71 min, [M+H]+=425/427. 1H NMR (DMSO-d6): 11.68 (1H, s), 10.46 (1H, s), 8.35 (1H, d, J=0.79 Hz), 7.95 (1H, d, J=7.36 Hz), 7.78 (1H, d, J=2.27 Hz), 7.42 (1H, dd, J=8.62, 2.29 Hz), 7.01 (1H, d, J=8.63 Hz), 6.79 (1H, d, J=7.35 Hz), 6.56 (1H, s), 4.69 (1H, s), 3.87 (2H, t, J=4.89 Hz), 3.57 (2H, m).

Workup

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

Sources & evidence

ORD record
ord-8712c3f2a38f410584813cb7656d39e4
Source dataset
uspto-grants-2012_10
Patent number
US08293763B2

Reaction notes

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