Hydrochloric Acid → 4-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-5-carboxylic acid ((R)-2,3-dihydroxy-propoxy)-amide

HRID 79074Notes

Reaction equation

HRID 79074 reaction equation
CC1(C)[O:6][C@@H:5]([CH2:7][O:8][NH:9][C:10]([C:12]2[CH:13]=[CH:14][C:15]3[S:19][N:18]=[CH:17][C:16]=3[C:20]=2[NH:21][C:22]2[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=2[F:29])=[O:11])[CH2:4][O:3]1.Cl>CO.O1CCOCC1>[OH:6][C@H:5]([CH2:4][OH:3])[CH2:7][O:8][NH:9][C:10]([C:12]1[CH:13]=[CH:14][C:15]2[S:19][N:18]=[CH:17][C:16]=2[C:20]=1[NH:21][C:22]1[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=1[F:29])=[O:11]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86656249HCID 86656249, compound

Product 1

HCID 446032094-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-5-carboxylic acid ((R)-2,3-dihydroxy-propoxy)-amideYield 56%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 4-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-5-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide (142 mg, 0.261 mmol) in MeOH (2 mL) was added a 4M HCl solution in dioxane (2 mL). The reaction mixture was stirred at room temperature for 2 hours before being concentrated in vacuo. The resultant residue was taken up in ethyl acetate, washed with a saturated aqueous solution of sodium hydrogen carbonate, water then brine, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was triturated in ethyl acetate/cyclohexane to afford the title compound as a solid (73 mg, 56%). LCMS (method A): RT=8.97 min, [M+H]+=504. NMR (DMSO-d6, 400 MHz) 11.78 (1 H, s), 9.28 (1 H, s), 8.64 (1 H, s), 7.84 (1 H, dd, J=8.48, 0.92 Hz), 7.64-7.57 (2 H, m), 7.31 (1 H, dd, J=8.47, 1.83 Hz), 6.65 (1 H, t, J=8.71 Hz), 4.80 (1 H, s), 4.54 (1 H, s), 3.80 (1 H, t, J=6.46 Hz), 3.68-3.61 (2 H, m), 3.32 (2 H, s).

Workup

  1. concentrationbefore being concentrated in vacuo
  2. washwashed with a saturated aqueous solution of sodium hydrogen carbonate, water
  3. dry with materialbrine, dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was triturated in ethyl acetate/cyclohexane

Sources & evidence

ORD record
ord-1a5e5c0b699a4c49b71beef8e33464f9
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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