Tetrahydrofuran → 4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1958388Notes

Reaction equation

HRID 1958388 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].C1COCC1.Cl[C:23]1[N:28]=[CH:27][N:26]=[C:25]2[N:29]([C:32]3[CH:37]=[CH:36][C:35]([S:38]([CH3:41])(=[O:40])=[O:39])=[CH:34][C:33]=3[F:42])[N:30]=[CH:31][C:24]=12>C(Cl)Cl>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([O:16][C:23]2[N:28]=[CH:27][N:26]=[C:25]3[N:29]([C:32]4[CH:37]=[CH:36][C:35]([S:38]([CH3:41])(=[O:40])=[O:39])=[CH:34][C:33]=4[F:42])[N:30]=[CH:31][C:24]=23)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 218976614-Chloro-1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidine

Product 1

HCID 536303944-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 500 mL round-bottomed flask equipped with a N2 inlet septum was placed a stir bar, NaH (60% in mineral oil, 1.8 g, 45.6 mmol) and 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (1.53 g, 7.6 mmol). THF (anhydrous, 80 mL) was added to the mixture. The resulting suspension was stirred about 30 min at room temperature. 4-Chloro-1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidine (2.5 g, 7.6 mmol) was then added in one portion. The mixture was stirred overnight under N2 at room temperature and the resulting slurry turned slightly yellowish. The slurry was added CH2Cl2 and filtered. The filtrate was concentrated under vacuum to give the crude product. Column chromatography purification using 50% EtOAc/Hexane gave Compound A74 as an off-white solid. Exact mass calculated for C22H26FN5O5S: 491.16, found 492.1 (MH+).

Workup

  1. customIn a 500 mL round-bottomed flask equipped with a N2 inlet septum
  2. stirringThe mixture was stirred overnight under N2 at room temperature
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated under vacuum

Sources & evidence

ORD record
ord-1f4e6937a0114eb5836c7d02a71c376f
Source dataset
uspto-grants-2013_04
Patent number
US08410119B2

Reaction notes

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