Hydrochloric Acid → 3-(2-Fluoro-4-iodo-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid (2-hydroxyethoxy)-amide

HRID 1366789Notes

Reaction equation

HRID 1366789 reaction equation
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[S:18][C:17]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[C:11]=1[NH:19][C:20]1[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=1[F:27])=[O:9])=C.Cl>C(O)C>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[S:18][C:17]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[C:11]=1[NH:19][C:20]1[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=1[F:27])=[O:9]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 25029778HCID 25029778, compound

Product 1

HCID 250297793-(2-Fluoro-4-iodo-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid (2-hydroxyethoxy)-amideYield 40%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

3-(2-Fluoro-4-iodo-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide (91 mg, 0.18 mmol) was dissolved in ethanol (2 ml) and 1M hydrochloric acid (0.5 ml) added. The mixture was allowed to stir for 2 hours then evaporated to dryness to give a residue. The resultant residue was partitioned between aqueous saturated NaHCO3 solution (3 ml), water (20 ml) and DCM (20 ml). The organic layer was separated, dried over sodium sulfate, filtered and evaporated to give a yellow solid. The resultant yellow solid was purified by flash chromatography (Si-SPE, DCM:MeOH, gradient 100:0 to 98:2) followed by reversed phase HPLC (Phenomenex Luna 5 phenyl/hexyl, 0.1% TFA in water on a gradient of methanol 95:5 to 40:60) to afford the title compound as a yellow solid (34 mg, 40%). LCMS (method A): RT=6.00 min, M+H+=474. 1H NMR (d4-MeOH, 400 MHz) 8.68 (s, 1H), 8.44 (d, J=5.7 Hz, 1H), 7.98 (dd, J=5.7 Hz, 0.8 Hz, 1H), 7.55 (dd, J=10.5 Hz, 1.8 Hz, 1H), 7.35-7.40 (m, 1H), 6.7 (dd, J=8.5 Hz, 8.5 Hz, 1H), 3.98 (t, J=Hz, 2H), 3.74 (t, J=Hz, 2H).

Workup

  1. customthen evaporated to dryness
  2. customto give a residue
  3. customThe resultant residue was partitioned between aqueous saturated NaHCO3 solution (3 ml), water (20 ml) and DCM (20 ml)
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customto give a yellow solid
  9. customThe resultant yellow solid was purified by flash chromatography (Si-SPE, DCM:MeOH, gradient 100:0 to 98:2)

Sources & evidence

ORD record
ord-f2edef031d8b4bad86409112d6e3ab03
Source dataset
uspto-grants-2011_02
Patent number
US07893085B2

Reaction notes

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