Sodium hydride → 4-(3,5-Dimethylpiperidino)-6-(2-pentynyloxy)pyrimidine

HRID 14524

Reaction equation

HRID 14524 reaction equation
[H-].[Na+].[CH2:3]([OH:8])[C:4]#[C:5][CH2:6][CH3:7].Cl[C:10]1[CH:15]=[C:14]([N:16]2[CH2:21][CH:20]([CH3:22])[CH2:19][CH:18]([CH3:23])[CH2:17]2)[N:13]=[CH:12][N:11]=1.[Cl-].[NH4+]>O1CCCC1>[CH3:23][CH:18]1[CH2:19][CH:20]([CH3:22])[CH2:21][N:16]([C:14]2[CH:15]=[C:10]([O:8][CH2:3][C:4]#[C:5][CH2:6][CH3:7])[N:11]=[CH:12][N:13]=2)[CH2:17]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 804212-Pentyn-1-olHCID 593411264-Chloro-6-(3,5-dimethylpiperidin-1-yl)pyrimidine

Product 1

HCID 578246824-(3,5-Dimethylpiperidino)-6-(2-pentynyloxy)pyrimidineYield 41.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

0.07 g of sodium hydride (60% oil suspension) was suspended in 2 ml of tetrahydrofuran. 0.5 ml of tetrahydrofuran solution of 0.13 g of 2-pentyn-1-ol was added dropwise at 0° C. therein, and the mixture was stirred for 10 minutes. Into the mixture was added dropwise 0.5 ml of tetrahydrofuran solution of 0.3 g of 4-chloro-6-(3,5-dimethylpiperidino)pyrimidine obtained the Reference Production Example 6, and stirred for 6 hours at room temperature. Into the reaction mixture was added a saturated ammonium chloride aqueous solution, and the mixture was extracted with tert-butyl methyl ether three times. The organic layers were washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to obtain 0.15 g of 4-(3,5-dimethylpiperidino)-6-(2-pentynyloxy)pyrimidine (hereinafter, referred to as Compound (15)). Compound (15) had the cis/trans diastereomer originated two methyls on the pyperidine ring. The ratio of the cis/trans diastereomer was about 8.2/1.

Workup

  1. customobtained the Reference Production Example 6
  2. stirringstirred for 6 hours at room temperature
  3. extractionthe mixture was extracted with tert-butyl methyl ether three times
  4. washThe organic layers were washed with a saturated sodium chloride aqueous solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-a79edb2402154df9a2308df6ce7e15a5
Source dataset
uspto-grants-2010_06
Patent number
US07732448B2

Linked notes

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