Trifluoroacetic acid → HCID 86719974, compound

HRID 1617334Notes

Reaction equation

HRID 1617334 reaction equation
COC[N:4]1[C:8]2[CH:9]=[CH:10][C:11]([CH:13]([C:15]3[CH:19]=[CH:18][N:17]([C:20]4[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][O:29]C5CCCCO5)=[CH:22][N:21]=4)[N:16]=3)[CH3:14])=[CH:12][C:7]=2[S:6][C:5]1=[O:36].FC(F)(F)C(O)=O.C1COCC1.[OH-].[NH4+]>CCOC(C)=O>[OH:29][CH2:28][CH2:27][O:26][C:23]1[CH:24]=[CH:25][C:20]([N:17]2[CH:18]=[CH:19][C:15]([CH:13]([C:11]3[CH:10]=[CH:9][C:8]4[NH:4][C:5](=[O:36])[S:6][C:7]=4[CH:12]=3)[CH3:14])=[N:16]2)=[N:21][CH:22]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8028TetrahydrofuranHCID 14923Ammonium HydroxideHCID 86719973HCID 86719973, compound

Product 1

HCID 86719974HCID 86719974, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
72 °C

Procedure

Dissolve 3-(methoxymethyl)-6-{1-[1-(5-{2-(tetrahydro-2H-pyran-2-yloxy)ethoxy}pyridine-2-yl)-1H-pyrazol-3-yl]ethyl}-3H-1,3-benzothiazol-2-one (140 mg, 274.18 μmoles) in trifluoroacetic acid (0.05 M; 73 mmoles; 5.5 mL) and heat at reflux (˜72° C.) under N2 for 2 hr. (orange color observed after about 10 min. and at 70° C.). Cool the reaction to room temperature and concentrate under reduced pressure. Dissolve the residue in THF (0.05 M; 67 mmoles, 5.5 mL), add 28% ammonium hydroxide (0.2 M; 9.9 mmoles; 1.4 mL), and stir at room temperature for ˜1 hr. Dilute with EtOAc (100 ml), wash with brine, dry over sodium sulfate, filter and concentrate. Purify by liquid chromatography on a 25 g silica gel column, eluting with a gradient of 60-80% EtOAc in hexanes to give 6-(1-{1-[5-(2-hydroxy-ethoxy)-pyridin-2-yl]-1H-pyrazol-3-yl}-ethyl)-3H-1,3-benzothiazol-2-one as a white foam (80 mg; 209 μmoles; 76% yield). LCMS (Low) rt 1.8 min., M+1=383.

Workup

  1. temperatureheat
  2. custom(orange color observed after about 10 min. and at 70° C.)
  3. temperatureCool
  4. customthe reaction to room temperature
  5. concentrationconcentrate under reduced pressure
  6. washwash with brine
  7. dry with materialdry over sodium sulfate
  8. filtrationfilter
  9. concentrationconcentrate
  10. customPurify by liquid chromatography on a 25 g silica gel column
  11. washeluting with a gradient of 60-80% EtOAc in hexanes

Sources & evidence

ORD record
ord-b26f2fd3add84939bd9c90f91ccb29e2
Source dataset
uspto-grants-2014_07
Patent number
US08765960B2

Reaction notes

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