Trifluoroacetic acid → [(2Z)-2-[4-[4-chloro-2-(2-methylpyrazol-3-yl)phenoxy]-3-cyanophenyl]sulfonylimino-1,3-thiazol-3-yl]methyl dihydrogen phosphate

HRID 46275Notes

Reaction equation

HRID 46275 reaction equation
[P:1]([O:13][CH2:14][N:15]1[CH:19]=[CH:18][S:17]/[C:16]/1=[N:20]\[S:21]([C:24]1[CH:29]=[CH:28][C:27]([O:30][C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=2[C:38]2[N:42]([CH3:43])[N:41]=[CH:40][CH:39]=2)=[C:26]([C:44]#[N:45])[CH:25]=1)(=[O:23])=[O:22])([O:8]C(C)(C)C)([O:3]C(C)(C)C)=[O:2].FC(F)(F)C(O)=O>C(OCC)(=O)C.ClCCl.C(O)C.CO>[P:1]([OH:8])([OH:3])([O:13][CH2:14][N:15]1[CH:19]=[CH:18][S:17]/[C:16]/1=[N:20]\[S:21]([C:24]1[CH:29]=[CH:28][C:27]([O:30][C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=2[C:38]2[N:42]([CH3:43])[N:41]=[CH:40][CH:39]=2)=[C:26]([C:44]#[N:45])[CH:25]=1)(=[O:22])=[O:23])=[O:2]

Participants

7

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 59436487ditert-butyl [(2Z)-2-[4-[4-chloro-2-(2-methylpyrazol-3-yl)phenoxy]-3-cyanophenyl]sulfonylimino-1,3-thiazol-3-yl]methyl phosphate

Product 1

HCID 59436471[(2Z)-2-[4-[4-chloro-2-(2-methylpyrazol-3-yl)phenoxy]-3-cyanophenyl]sulfonylimino-1,3-thiazol-3-yl]methyl dihydrogen phosphate

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Di-tert-butyl [(2Z)-2-[({4-[4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenoxy]-3-cyanophenyl}sulfonyl)imino]-1,3-thiazol-3(2H)-yl]methyl phosphate, (Example 1040, 250 mg, 0.00036 mol) was dissolved in ethyl acetate (10 mL) and then trifluoroacetic acid (1 mL) was added. The solution was stirred at room temperature for 3 hours, then a further portion of trifluoroacetic acid (2 mL) was added and stirred at room temperature for 18 hours. The solvents were removed in vacuo and the residue was partitioned between tert-butylmethyl ether (30 mL) and water (40 mL) and a few drops of aqueous sodium hydroxide solution (2 molar). The aqueous layer was then acidified to pH 1-2 with aqueous hydrochloric acid (2 molar) to give a sticky cream precipitate which was dissolved in a mixture of dichloromethane, ethanol and methanol. This organic layer was dried over anhydrous sodium sulphate, filtered and the solvents removed in vacuo to give the crude product which was triturated with ethyl acetate to give the title compound as a buff powder, (85 mg).

Workup

  1. stirringstirred at room temperature for 18 hours
  2. customThe solvents were removed in vacuo
  3. customthe residue was partitioned between tert-butylmethyl ether (30 mL) and water (40 mL) and a few drops of aqueous sodium hydroxide solution (2 molar)
  4. customto give a sticky cream precipitate which
  5. dry with materialThis organic layer was dried over anhydrous sodium sulphate
  6. filtrationfiltered
  7. customthe solvents removed in vacuo
  8. customto give the crude product which
  9. customwas triturated with ethyl acetate

Sources & evidence

ORD record
ord-b9e73e81fd044053be27216c3a342cbe
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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