7-Fluoro-3-(2-fluoro-4-iodo-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide → 7-Fluoro-3-(2-fluoro-4-iodo-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid (2-hydroxy-ethoxy)-amide

HRID 1366794Notes

Reaction equation

HRID 1366794 reaction equation
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[S:18][C:17]2[C:16]([F:19])=[CH:15][N:14]=[CH:13][C:12]=2[C:11]=1[NH:20][C:21]1[CH:26]=[CH:25][C:24]([I:27])=[CH:23][C:22]=1[F:28])=[O:9])=C>CO.C(Cl)Cl>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[S:18][C:17]2[C:16]([F:19])=[CH:15][N:14]=[CH:13][C:12]=2[C:11]=1[NH:20][C:21]1[CH:26]=[CH:25][C:24]([I:27])=[CH:23][C:22]=1[F:28])=[O:9]

Participants

4

Reactant 1

HCID 597038727-Fluoro-3-(2-fluoro-4-iodo-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide

Product 1

HCID 250297817-Fluoro-3-(2-fluoro-4-iodo-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid (2-hydroxy-ethoxy)-amideYield 53.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 7-fluoro-3-(2-fluoro-4-iodo-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide (100 mg, 0.19 mmol) in a mixture of methanol and DCM was loaded onto a 5 g SCX-2 cartridge, which was eluted with methanol followed by a 2M solution of ammonia in methanol. Appropriate fractions were combined and concentrated under reduced pressure. The residual solid was purified by column chromatography (Si-SPE, gradient 0-40% tert-butyl dimethyl ether in DCM then 10% methanol in DCM) to afford the title compound as a yellow solid (50 mg, 53%). LCMS (method A): RT=9.60 min, M+H+=492. 1H NMR (CD3OD, 400 MHz) 3.58 (2H, t, J=4.89 Hz), 3.84 (2H, t, J=4.91 Hz), 6.89 (1H, t, J=8.76 Hz), 6.98 (1H, dd, J=8.41, 2.15 Hz), 7.21-7.26 (1H, m), 8.02 (1H, d, J=5.61 Hz), 8.45 (1H, dd, J=8.25, 5.61 Hz), 8.53-8.59 (1H, m).

Workup

  1. washwas eluted with methanol
  2. concentrationconcentrated under reduced pressure
  3. customThe residual solid was purified by column chromatography (Si-SPE, gradient 0-40% tert-butyl dimethyl ether in DCM

Sources & evidence

ORD record
ord-176de735148e42ad889d6e1c26dc1da1
Source dataset
uspto-grants-2011_02
Patent number
US07893085B2

Reaction notes

Loading…