Water → 4-(4-Fluoro-3-trifluoromethyl-benzoyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide

HRID 550813Notes

Reaction equation

HRID 550813 reaction equation
Cl.[CH3:2][O:3][C:4]1[C:5]2[N:12]=[C:11]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[O:15])[S:10][C:6]=2[N:7]=[CH:8][N:9]=1.[F:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27]Cl)=[CH:25][C:24]=1[C:31]([F:34])([F:33])[F:32].C(N(CC)CC)C.[OH2:42]>C(Cl)Cl>[CH3:2][O:3][C:4]1[C:5]2[N:12]=[C:11]([NH:13][C:14]([N:16]3[CH2:17][CH2:18][N:19]([C:27](=[O:42])[C:26]4[CH:29]=[CH:30][C:23]([F:22])=[C:24]([C:31]([F:34])([F:33])[F:32])[CH:25]=4)[CH2:20][CH2:21]3)=[O:15])[S:10][C:6]=2[N:7]=[CH:8][N:9]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 27591684-(Chloromethyl)-1-fluoro-2-(trifluoromethyl)benzeneHCID 86616506Piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide hydrochloride

Product 1

HCID 248317244-(4-Fluoro-3-trifluoromethyl-benzoyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amideYield 30.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide hydrochloride (as prepared in Example 1, 300 mg, 0.91 mmol), 4-fluoro-3-(trifluoromethyl)benzyl chloride (140 mL, 0.92 mmol) and triethylamine (3.4 mL, 2.27 mmol) in methylene chloride (15 mL) was stirred overnight at 25° C. At this time, the reaction was poured into water and was extracted into ethyl acetate. The combined organics were washed with a saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. The resulting solids were recrystallized twice from 2:1:1 methanol/dimethylsulfoxide/dioxane to afford 4-(4-fluoro-3-trifluoromethyl-benzoyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (134 mg, 30.5%) as white solid; ES-HRMS m/e calcd for C19H16F4N6O3S (M+H)+ 485.1014, found 485.1014.

Workup

  1. extractionwas extracted into ethyl acetate
  2. washThe combined organics were washed with a saturated aqueous sodium bicarbonate solution
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting solids were recrystallized twice from 2:1:1 methanol/dimethylsulfoxide/dioxane

Sources & evidence

ORD record
ord-5e65efd63d69451c899c7a2245b7ff1b
Source dataset
uspto-grants-2011_05
Patent number
US07947692B2

Reaction notes

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