Sodium hydride → 4-[4-(4-Methanesulfonyl-phenoxy)-3-methyl-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester

HRID 1931631Notes

Reaction equation

HRID 1931631 reaction equation
[H-].[Na+].[CH3:3][S:4]([C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)(=[O:6])=[O:5].[CH:14]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([N:26]2[C:30]3=[N:31][CH:32]=[N:33][C:34](Cl)=[C:29]3[C:28]([CH3:36])=[N:27]2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])[CH3:15].[Cl-].[NH4+]>CN(C)C=O>[CH:14]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([N:26]2[C:30]3=[N:31][CH:32]=[N:33][C:34]([O:13][C:10]4[CH:11]=[CH:12][C:7]([S:4]([CH3:3])(=[O:5])=[O:6])=[CH:8][CH:9]=4)=[C:29]3[C:28]([CH3:36])=[N:27]2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])[CH3:15]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 1233504-(Methylsulfonyl)phenolHCID 579649474-(4-Chloro-3-methyl-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylic acid isopropyl ester2×

Product 1

HCID 579650154-[4-(4-Methanesulfonyl-phenoxy)-3-methyl-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl esterYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (60% dispersion in mineral oil; 7 mg, 0.18 mmol) was added to a solution of 4-(methylsulfonyl)phenol (20 mg, 0.12 mmol) in dimethylformamide (1 mL) and the mixture was stirred at room temperature for 15 min. A solution of 4-(4-chloro-3-methyl-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid isopropyl ester (Intermediate 21; 40 mg, 0.12 mmol) in dimethylformamide (1 mL) was added, and the reaction mixture was allowed to stir at room temperature overnight. Saturated aqueous ammonium chloride solution was added and the mixture was extracted with ethyl acetate (3×25 mL). The organic layer was washed with water (3 times) and brine, dried (sodium sulfate), filtered, evaporated and purified on a flash silica column (20 mm×3″) eluting with 75-80% ethyl acetate/hexanes to give 4-[4-(4-methanesulfonyl-phenoxy)-3-methyl-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester (38 mg, 68%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 1.20 (d, 6H, J=6.3 Hz), 1.93-2.02 (m, 4H), 2.62 (s, 3H), 3.03-3.09 (m, 2H), 3.32 (s, 3H), 4.08-4.12 (m, 2H), 4.77-4.81 (m, 1H), 4.85-4.95 (m, 1H), 7.59-7.62 (m, 2H), 8.01-8.04 (m, 2H), 8.46 (s, 1H). Mass spectrum (ES) MH+=474.

Workup

  1. stirringto stir at room temperature overnight
  2. extractionthe mixture was extracted with ethyl acetate (3×25 mL)
  3. washThe organic layer was washed with water (3 times) and brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified on a flash silica column (20 mm×3″)
  8. washeluting with 75-80% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-136fc32cf36045d1a7cb5393305014c2
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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