Trifluoroacetic acid → HCID 66780118, compound

HRID 1958049Notes

Reaction equation

HRID 1958049 reaction equation
[Cl:1][C:2]1[C:3]([CH3:34])=[C:4]([CH2:8][N:9]2[C:14]3[N:15]=[C:16]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[S:17][C:13]=3[C:12](=[O:24])[N:11]=[C:10]2[S:25][CH2:26][C:27]([O:29]C(C)(C)C)=[O:28])[CH:5]=[CH:6][CH:7]=1.C(O)(C(F)(F)F)=O>ClCCl>[Cl:1][C:2]1[C:3]([CH3:34])=[C:4]([CH2:8][N:9]2[C:14]3[N:15]=[C:16]([N:18]4[CH2:19][CH2:20][O:21][CH2:22][CH2:23]4)[S:17][C:13]=3[C:12](=[O:24])[N:11]=[C:10]2[S:25][CH2:26][C:27]([OH:29])=[O:28])[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68041347HCID 68041347, compound

Product 1

HCID 66780118HCID 66780118, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1-dimethylethyl {[4-[(3-chloro-2-methylphenyl)methyl]-2-(4-morpholinyl)-7-oxo-4,7-dihydro[1,3]thiazolo[4,5-d]pyrimidin-5-yl]thio}acetate (182 mg, 0.348 mmol) in Dichloromethane (DCM) (2 mL) in a 20 mL Scintillation vial stirred at rt was added TFA (2 mL, 26.0 mmol). After sitting at rt for 5 hr LC/MS analysis indicated complete conversion to the acid. The DCM/TFA was removed in vacuo and the resulting residue was taken up in DCM. Attempts to extract the desired product into 1 N NaOH solution led to emulsions, so the pH was adjusted to 2 and the DCM layer was concentrated and to the residue was added water and the resultant solid was isolated by filtration and then purified by reverse phase prep HPLC on 30 mm prep column eluting with a gradient 25% to 55% AcCN over 12 minutes. LC/MS (ES) m/z=467 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 7.35 (d, 1H), 7.09 (t, 1H), 6.61 (d, 1H), 5.56 (s, 2H), 4.01 (s, 2H), 3.83 (m, 4H), 3.59 (m, 4H), 2.49 (s, 3H).

Workup

  1. customThe DCM/TFA was removed in vacuo
  2. extractionto extract the desired product into 1 N NaOH solution
  3. concentrationthe DCM layer was concentrated and to the residue
  4. additionwas added water
  5. customthe resultant solid was isolated by filtration
  6. custompurified by reverse phase prep HPLC on 30 mm prep column
  7. washeluting with a gradient 25% to 55% AcCN over 12 minutes

Sources & evidence

ORD record
ord-af74c1345ec04211980ff53874efdd5d
Source dataset
uspto-grants-2013_04
Patent number
US08410095B2

Reaction notes

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