Hydrochloric Acid → 7-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-6-carboxylic acid ((R)-2,3-dihydroxy-propoxy)amide

HRID 79084Notes

Reaction equation

HRID 79084 reaction equation
CC1(C)[O:6][C@@H:5]([CH2:7][O:8][NH:9][C:10]([C:12]2[CH:20]=[CH:19][C:15]3[CH:16]=[N:17][S:18][C:14]=3[C:13]=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>[OH:6][C@H:5]([CH2:4][OH:3])[CH2:7][O:8][NH:9][C:10]([C:12]1[CH:20]=[CH:19][C:15]2[CH:16]=[N:17][S:18][C:14]=2[C:13]=1[NH:21][C:22]1[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=1[F:29])=[O:11]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 575215077-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-6-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

Product 1

HCID 446033417-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-6-carboxylic acid ((R)-2,3-dihydroxy-propoxy)amideYield 53%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 7-(2-fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-6-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide (263 mg, 0.48 mmol) in MeOH (10 mL) was added a 1.0M aqueous solution of hydrochloric acid (0.97 mL). The reaction mixture was stirred at room temperature for 18 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 then brine, dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0% to 100%, ethyl acetate in DCM) to afford the title compound as a yellow solid (127 mg, 53%). LCMS (method A): RT=9.05 min, [M+H]+=504. 1H NMR (CD3OD, 400 MHz) 8.88 (1 H, s), 7.74 (1 H, d, J=8.36 Hz), 7.61 (1 H, d, J=8.35 Hz), 7.53 (1 H, dd, J=10.01, 1.93 Hz), 7.44 (1 H, ddd, J=8.36, 1.93, 1.06 Hz), 6.76 (1 H, t, J=8.53 Hz), 4.05 (1 H, dd, J=10.03, 3.50 Hz), 3.96-3.83 (2 H, m), 3.63-3.52 (2 H, m).

Workup

  1. concentrationbefore being concentrated in vacuo
  2. washwashed with a saturated aqueous solution of sodium hydrogen carbonate
  3. dry with materialbrine, dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-1770e3186a5f4add9d724c2bef40182f
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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