Hydrochloric Acid → HCID 178461689, compound

HRID 1094328Notes

Reaction equation

HRID 1094328 reaction equation
II.[S:3]=[C:4]([C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18]2[S:19][CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[N:22]=2)=[CH:13][CH:12]=1)[CH3:10])[CH2:5][C:6]([NH2:8])=[O:7].C([O-])([O-])=O.[K+].[K+].Cl>CCO.O>[F:24][C:23]([F:25])([F:26])[C:21]1[N:22]=[C:18]([NH:17][C:14]2[CH:13]=[CH:12][C:11]([C@H:9]([C:4]3[S:3][N:8]=[C:6]([OH:7])[CH:5]=3)[CH3:10])=[CH:16][CH:15]=2)[S:19][CH:20]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 807IodineHCID 11430Potassium CarbonateHCID 86645981HCID 86645981, compound

Product 1

HCID 178461689HCID 178461689, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent

Procedure

A solution of iodine (135 mg, 0.53 mmol) in EtOH (5 ml) was added dropwise to a cooled mixture (0-5° C.) of the intermediate 12b (150 mg, 0.40 mmol) and K2CO3 (212 mg, 1.53 mmol) in EtOH (5 ml). The reaction mixture was stirred for 24 h at room temperature. Water (10 ml) was added and pH adjusted to 3 by 1M HCl. The aqueous layer was extracted with EtOAc (3×10 ml); the collected organic extracts were dried over anhydrous Na2SO4 and, after solvent evaporation, the purification of the crude by flash chromatography (CH2Cl2/CH3OH 95:5) afforded 5-[(1R)-1-(4-{[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino}phenyl)ethyl]isothiazol-3-ol (12) (82 mg, 0.22 mmol) as a white solid (41%). [α]D=−31 (c=1; CH3OH); 1H-NMR (CDCl3): δ 10.60 (bs, 1H, OH), 9.15 (bs, 1H, NH), 7.40 (d, 2H, J=7 Hz), 7.25 (d, 2H, J=7 Hz), 7.00 (s, 1H), 5.50 (s, 1H), 3.80 (q, 1H, J=7 Hz), 1.55 (d, 3H, J=7 Hz).

Workup

  1. extractionThe aqueous layer was extracted with EtOAc (3×10 ml)
  2. dry with materialthe collected organic extracts were dried over anhydrous Na2SO4
  3. customafter solvent evaporation
  4. customthe purification of the crude by flash chromatography (CH2Cl2/CH3OH 95:5)

Sources & evidence

ORD record
ord-ca9d73cd4bda479280e683c48dcacb1d
Source dataset
uspto-grants-2012_03
Patent number
US08133911B2

Reaction notes

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