Hydrochloric Acid → 3-(2-Fluoro-4-iodo-phenylamino)-1-(2-hydroxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid amide

HRID 2264963Notes

Reaction equation

HRID 2264963 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:14]2[CH:15]=[N:16][CH:17]=[CH:18][C:13]=2[N:12]([CH2:19][CH2:20][O:21][Si](C(C)C)(C(C)C)C(C)C)[C:11]=1[C:32]([NH2:34])=[O:33].Cl>CO>[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:14]2[CH:15]=[N:16][CH:17]=[CH:18][C:13]=2[N:12]([CH2:19][CH2:20][OH:21])[C:11]=1[C:32]([NH2:34])=[O:33]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 595964823-(2-Fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid amide

Product 1

HCID 249481373-(2-Fluoro-4-iodo-phenylamino)-1-(2-hydroxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid amideYield 53.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of 3-(2-fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid amide (100 mg, 0.17 mmol) in methanol was added a 1M solution of HCl (0.34 mL, 0.34 mmol). The reaction mixture was heated at reflux and stirred for 1 hour. After cooling to room temperature the reaction mixture was passed through a 5 g SCX-2 cartridge eluting with MeOH then 2M solution of ammonia in MeOH. The appropriate fractions were combined and concentrated to give a residue that was purified by flash chromatography (Si-PPC, MeOH:DCM, gradient 0:100 to 20:80) to provide the title compound as an off-white solid (40 mg, 53%). LCMS (method A): RT=5.78 min, M+H+=441. 1H NMR (DMSO-D6) 3.70 (2H, q, J=5.3 Hz), 4.53 (2H, t, J=5.3 Hz), 4.94 (1H, t, J=5.3 Hz), 6.19 (1H, t, J=8.9 Hz), 7.20 (1H, m), 7.53 (1H, dd, J=11.0, 2.0 Hz), 7.60 (1H, dd, J=6.0, 1.0 Hz), 7.72 (1H, d, J=2.0 Hz), 7.81 (2H, s, br), 8.28 (1H, d, J=6.0 Hz), 8.52 (1H, d, J=1.0 Hz).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux
  3. washeluting with MeOH
  4. concentrationconcentrated
  5. customto give a residue that
  6. customwas purified by flash chromatography (Si-PPC, MeOH:DCM, gradient 0:100 to 20:80)

Sources & evidence

ORD record
ord-aa4c0d153b1646838ceb61efb62767c2
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

Loading…