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

HRID 79078Notes

Reaction equation

HRID 79078 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]([Br: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]([Br:28])=[CH:24][C:23]=1[F:29])=[O:11]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 866562517-(4-bromo-2-fluoro-phenylamino)-benzo[d]isothiazole-6-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

Product 1

HCID 446032697-(4-Bromo-2-fluoro-phenylamino)-benzo[d]isothiazole-6-carboxylic acid ((R)-2,3-dihydroxy-propoxy)-amideYield 71%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 7-(4-bromo-2-fluoro-phenylamino)-benzo[d]isothiazole-6-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide (370 mg, 0.75 mmol) in MeOH (4 mL) was added a 1.0M aqueous solution of hydrochloric acid (1.50 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 then brine, dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0% to 100%, MeOH in DCM) to afford the title compound as a yellow solid (242 mg, 71%). LCMS (method A): RT=8.80 min, [M+H]+=456/458. 1H NMR (CD3OD, 400 MHz) 8.87 (1 H, s), 7.76-7.70 (1 H, m), 7.61 (1 H, d, J=8.36 Hz), 7.42-7.36 (1 H, m), 7.30-7.25 (1 H, m), 6.95 (1 H, t, J=8.66 Hz), 4.06 (1 H, dd, J=10.08, 3.55 Hz), 3.96-3.83 (2 H, m), 3.64-3.54 (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-627d84f0719e43a1a8608bdf3c416a08
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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