Potassium Hydroxide → HCID 67487542, compound

HRID 1809620Notes

Reaction equation

HRID 1809620 reaction equation
[CH3:1][C:2]1[C:7]([O:8][C:9]2[C:10]([NH:19][C:20]3[S:24][N:23]=[C:22]([CH:25]4[CH2:31][CH:30]5[N:32](C(OCC)=O)[CH:27]([CH2:28][CH2:29]5)[CH2:26]4)[N:21]=3)=[N:11][CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[OH-].[K+]>CC(O)C.O>[CH:30]12[NH:32][CH:27]([CH2:28][CH2:29]1)[CH2:26][CH:25]([C:22]1[N:21]=[C:20]([NH:19][C:10]3[C:9]([O:8][C:7]4[C:2]([CH3:1])=[N:3][CH:4]=[CH:5][CH:6]=4)=[CH:14][C:13]([C:15]([F:16])([F:17])[F:18])=[CH:12][N:11]=3)[S:24][N:23]=1)[CH2:31]2

Participants

5

Reactant 2

HCID 14797Potassium Hydroxide2×HCID 67487872Ethyl 3-(5-(3-(2-methylpyridin-3-yloxy)-5-(trifluoromethyl)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

Product 1

HCID 67487542HCID 67487542, compoundYield 74.8%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 3776IsopropanolSolvent

Procedure

Ethyl 3-(5-(3-(2-methylpyridin-3-yloxy)-5-(trifluoromethyl)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate (69.5 mg, 0.130 mmol) was dissolved in iPrOH (5 mL) and potassium hydroxide (72.9 mg, 1.30 mmol) was added. The reaction was heated to reflux for 3 days. More KOH (72.9 mg, 1.30 mmol) was added and the reaction was heated for another 2 days. Water (˜10 drops) was added and the reaction was heated for 1 week. The solution was partitioned between saturated aqueous NH4Cl and CH2Cl2. The aqueous layer was extracted 3 times with CH2Cl2, dried over sodium sulfate, filtered and concentrated to afford crude 3-(8-azabicyclo[3.2.1]octan-3-yl)-N-(3-(2-methylpyridin-3-yloxy)-5-(trifluoromethyl)pyridin-2-yl)-1,2,4-thiadiazol-5-amine (45 mg, 0.0973 mmol, 74.8% yield).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 3 days
  3. temperaturethe reaction was heated for another 2 days
  4. temperaturethe reaction was heated for 1 week
  5. customThe solution was partitioned between saturated aqueous NH4Cl and CH2Cl2
  6. extractionThe aqueous layer was extracted 3 times with CH2Cl2
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-7965046f49b549b89f7f507aee92ab31
Source dataset
uspto-grants-2013_01
Patent number
US08362037B2

Reaction notes

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