Sulfuric Acid → HCID 59011947, compound

HRID 550822Notes

Reaction equation

HRID 550822 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.[Cl:32][CH2:33][C:34]#[N:35].S(=O)(=O)(O)[OH:37]>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:35][C:34](=[O:37])[CH2:33][Cl:32])([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

6

Reactant 3

HCID 1118Sulfuric AcidHCID 7856ChloroacetonitrileHCID 24829619HCID 24829619, compound

Product 1

HCID 59011947HCID 59011947, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 4-hydroxy-4-(3-trifluoromethyl-phenyl)-piperidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (prepared as in Example 65, 114 mg, 0.25 mmol) in acetic acid (0.24 mL) was treated with chloroacetonitrile (0.20 mL, 3.10 mmol). The resulting mixture was sonicated in a water bath until all the solid dissolved and then was cooled to 0° C. The reaction was then treated with concentrated sulfuric acid (0.24 mL) at 0° C. Upon complete addition, the reaction was warmed to 25° C. and was stirred at 25° C. for 2 h. At this time, the mixture was diluted with water and was extracted with ethyl acetate. The organics were washed with a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo. The resulting material was triturated with diethyl ether to afford 4-(2-chloro-acetylamino)-4-(3-trifluoromethyl-phenyl)-piperidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (88 mg, 67%) as an off-white solid. This material was used without further purification.

Workup

  1. customThe resulting mixture was sonicated in a water bath until all the solid
  2. dissolutiondissolved
  3. additionUpon complete addition
  4. temperaturethe reaction was warmed to 25° C.
  5. extractionwas extracted with ethyl acetate
  6. washThe organics were washed with a saturated aqueous sodium bicarbonate solution
  7. dry with materiala saturated aqueous sodium chloride solution, dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resulting material was triturated with diethyl ether

Sources & evidence

ORD record
ord-a53d111d933c4943a32ebcefa86dcb9a
Source dataset
uspto-grants-2011_05
Patent number
US07947692B2

Reaction notes

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