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Sodium hydride → 4-Hydroxy-4-[3-(trifluoromethy)phenyl]piperidine-1-carboxylic acid (7-methoxy-5-methylsulfanyl-thiazolo[5,4-d]pyrimidin-2-yl)-amide

HRID 550848
Notes
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Reaction equation

HRID 550848 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[N:13]=[C:12]([NH2:14])[S:11][C:5]=2[N:6]=[C:7]([S:9][CH3:10])[N:8]=1.[H-].[Na+].C(N(CC)C(C)C)(C)C.[OH:26][C:27]1([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([F:45])([F:44])[F:43])[CH:37]=2)[CH2:32][CH2:31][N:30]([C:33](Cl)=[O:34])[CH2:29][CH2:28]1>O1CCCC1>[CH3:1][O:2][C:3]1[C:4]2[N:13]=[C:12]([NH:14][C:33]([N:30]3[CH2:29][CH2:28][C:27]([OH:26])([C:36]4[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([F:44])([F:43])[F:45])[CH:37]=4)[CH2:32][CH2:31]3)=[O:34])[S:11][C:5]=2[N:6]=[C:7]([S:9][CH3:10])[N:8]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 81531DiisopropylethylamineHCID 590119344-Hydroxy4-[3-(trifluoromethyl)phenyl]piperidine-1-carbonyl chlorideHCID 590119397-Methoxy-5-methylsulfanyl-thiazolo[5,4-d]pyrimidin-2-ylamine

Product 1

HCID 590119534-Hydroxy-4-[3-(trifluoromethy)phenyl]piperidine-1-carboxylic acid (7-methoxy-5-methylsulfanyl-thiazolo[5,4-d]pyrimidin-2-yl)-amide
Yield 34.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A magnetically stirred mixture of 7-Methoxy-5-methylsulfanyl-thiazolo[5,4-d]pyrimidin-2-ylamine (500 mg, 2.19 mmol) in tetrahydrofuran (20 mL) under a nitrogen atmosphere at 25° C. was treated with sodium hydride (60% suspension in mineral oil, 265 mg, 6.58 mmol). The reaction mixture was stirred at 50° C. for 1 h. At this time, the reaction was cooled to room temperature and was treated with N,N-diisopropylethylamine (850 mg, 6.58 mmol) and 4-hydroxy-4-[3-(trifluoromethyl)phenyl]piperidine-1-carbonyl chloride (810 mg, 2.63 mmol). The reaction mixture was stirred at room temperature for 3 d. At this time, the reaction was concentrated in vacuo, poured into water and extracted with ethyl acetate. The organics were washed with a 2N aqueous hydrochloric acid solution and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 98:2 methylene chloride/methanol) afforded 4-hydroxy-4-[3-(trifluoromethy)phenyl]piperidine-1-carboxylic acid (7-methoxy-5-methylsulfanyl-thiazolo[5,4-d]pyrimidin-2-yl)-amide (375 mg, 34%) as a red solid. LRMS for C20H20F3N5O3S2 (M+H)+ at m/z=499. The NMR spectrum obtained on the sample is compatible with its structure.

Workup

  1. temperatureAt this time, the reaction was cooled to room temperature
  2. stirringThe reaction mixture was stirred at room temperature for 3 d
  3. concentrationAt this time, the reaction was concentrated in vacuo
  4. additionpoured into water
  5. extractionextracted with ethyl acetate
  6. washThe organics were washed with a 2N aqueous hydrochloric acid solution
  7. dry with materiala saturated aqueous sodium chloride solution, dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ea604829a2ff49f19987e54bfe88b4bc
Source dataset
uspto-grants-2011_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07947692B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes