1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 7-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-6-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

HRID 79083Notes

Reaction equation

HRID 79083 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:18]2[S:17][N:16]=[CH:15][C:14]=2[CH:13]=[CH:12][C:11]=1[C:19]([OH:21])=O.C(N(C(C)C)CC)(C)C.[CH3:31][C:32]1([CH3:40])[O:36][C@@H:35]([CH2:37][O:38][NH2:39])[CH2:34][O:33]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.C(OCC)(=O)C>[CH3:31][C:32]1([CH3:40])[O:36][C@@H:35]([CH2:37][O:38][NH:39][C:19]([C:11]2[CH:12]=[CH:13][C:14]3[CH:15]=[N:16][S:17][C:18]=3[C:10]=2[NH:9][C:3]2[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=2[F:1])=[O:21])[CH2:34][O:33]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11298047(R)-O-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)hydroxylamineHCID 575215047-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-6-carboxylic acid

Product 1

HCID 575215077-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-6-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amideYield 54%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 7-(2-fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-6-carboxylic acid (377 mg, 0.91 mmol) and diisopropylethylamine (0.47 mL, 2.73 mmol) in DMF (4 mL) were added O—((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-hydroxylamine (268 mg, 1.82 mmol), EDCI (349 mg, 1.82 mmol) and HOBt (246 mg, 1.82 mmol). The reaction mixture was stirred for 18 hours at room temperature, diluted with ethyl acetate, and washed with water, a saturated aqueous solution of sodium hydrogen carbonate, then brine before being dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0% to 100%, TBME in cyclohexane) to afford the title compound as a yellow solid (266 mg, 54%). LCMS (method B): RT=4.04 min, [M+H]+=544.

Workup

  1. washwashed with water
  2. dry with materiala saturated aqueous solution of sodium hydrogen carbonate, then brine before being dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-803283d825e04a468dd885c61934bee7
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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