Sulfuric Acid → HCID 24829959, compound

HRID 550821Notes

Reaction equation

HRID 550821 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[N:11]=[C:10]([NH:12][C:13]([N:15]3[CH2:20][CH2:19][C:18](O)([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=4)[CH2:17][CH2:16]3)=[O:14])[S:9][C:5]=2[N:6]=[CH:7][N:8]=1.S(=O)(=O)(O)O.C(=O)(O)[O-:38].[Na+].[C:42](#[N:44])[CH3:43]>C(O)(=O)C.O>[CH3:1][O:2][C:3]1[C:4]2[N:11]=[C:10]([NH:12][C:13]([N:15]3[CH2:20][CH2:19][C:18]([NH:44][C:42](=[O:38])[CH3:43])([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=4)[CH2:17][CH2:16]3)=[O:14])[S:9][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 6342AcetonitrileHCID 516892Sodium BicarbonateHCID 24829619HCID 24829619, compound

Product 1

HCID 24829959HCID 24829959, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 4-hydroxy-4-(3-trifluoromethyl-phenyl)-piperidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (prepared in Example 65, 100 mg, 0.22 mmol) in acetonitrile (0.16 mL) and glacial acetic acid (0.21 mL) cooled to 0 C was treated dropwise with concentrated sulfuric acid (0.21 mL). The resulting mixture was then allowed to warm to 25° C. After stirring for 2 h, the reaction mixture was diluted with water, neutralized with a saturated sodium bicarbonate solution and extracted with ethyl acetate. The extracts were dried over sodium sulfate, filtered and concentrated in vacuo. High pressure liquid chromatography (acetonitrile/0.1% trifluoroacetic acid/water gradient) followed by lyophilization of the desired fractions afforded 4-acetylamino-4-(3-trifluoromethyl-phenyl)-piperidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (37 mg, 28%) as a white powder; ES-HRMS m/e calcd. for C21H22N6O3SF3 (M+H)+ 495.1421, found 495.1424.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe extracts were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a2fb56994266411984c416ec3f3ad92e
Source dataset
uspto-grants-2011_05
Patent number
US07947692B2

Reaction notes

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