tert-Butanol → HCID 59013889, compound

HRID 907558Notes

Reaction equation

HRID 907558 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([NH:13][C:14]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[C:26](Cl)=[N:25][S:24][N:23]=3)[CH2:18][CH2:17]2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CC(C)([O-])C.[K+].C(O)(C)(C)C.[Cl:41][C:42]1[CH:47]=[C:46]([CH2:48][OH:49])[CH:45]=[CH:44][N:43]=1>CO>[F:28][C:2]([F:1])([F:29])[C:3]1[CH:4]=[C:5]([NH:13][C:14]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[C:26]([O:49][CH2:48][C:46]4[CH:45]=[CH:44][N:43]=[C:42]([Cl:41])[CH:47]=4)=[N:25][S:24][N:23]=3)[CH2:18][CH2:17]2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:8]=1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 7062237(2-Chloropyridin-4-yl)methanolHCID 23665647Potassium tert-butoxideHCID 590137964-(4-Chloro-[1,2,5]thiadiazol-3-yl)-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)amide

Product 1

HCID 59013889HCID 59013889, compoundYield 26.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 4-(4-chloro-[1,2,5]thiadiazol-3-yl)-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide (103.7 mg, 0.226 mmol, prepared in Example 10b) and 1M solution of potassium tert-butoxide in tert-butanol (0.70 mL, 0.70 mmol) was added 2-chloro-4-pyridinemethanol (64.5 mg, 0.448 mmol, prepared in Example 16a). The resulting suspension was stirred at room temperature for 2 h. The crude reaction mixture was diluted with methanol and purified by preparative HPLC (0.1% TFA in water, 0.1% TFA in acetonitrile). The pure fractions were combined and the acetonitrile/TFA was removed in vacuo. The remaining aqueous solution was made basic with NaHCO3 and the free based product was extracted into EtOAc. The organic phase was concentrated in vacuo yielding pure product N-[3,5-bis(trifluoromethyl)phenyl]-4-(4-{[(2-chloropyridin-4-yl)methyl]oxy}-1,2,5-thiadiazol-3-yl)piperazine-1-carboxamide (33.4 mg, 26.1% yield). 1H NMR (CDCl3) 8.43 (d, 1H), 7.90 (s, 2H), 7.55 (s, 1H), 7.38 (s, 1H), 6.68 (s, 1H), 5.49 (s, 2H), 3.66 (d, 8H) ppm.

Workup

  1. customThe crude reaction mixture
  2. custompurified by preparative HPLC (0.1% TFA in water, 0.1% TFA in acetonitrile)
  3. customthe acetonitrile/TFA was removed in vacuo
  4. extractionwas extracted into EtOAc
  5. concentrationThe organic phase was concentrated in vacuo

Sources & evidence

ORD record
ord-31c218a1b5234fcebaf5dea881a41177
Source dataset
uspto-grants-2011_09
Patent number
US08013156B2

Reaction notes

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