2-Butyn-1-ol → 1-(6-(2-butynyloxy)-5-fluoropyrimidin-4-yl)-cis-2,6-dimethyl-hexahydro-1H-azepine

HRID 1008707

Reaction equation

HRID 1008707 reaction equation
[H-].[Na+].[CH2:3]([OH:7])[C:4]#[C:5][CH3:6].Cl[C:9]1[N:14]=[CH:13][N:12]=[C:11]([N:15]2[CH2:21][C@H:20]([CH3:22])[CH2:19][CH2:18][CH2:17][C@@H:16]2[CH3:23])[C:10]=1[F:24].[Cl-].[NH4+]>O1CCCC1>[CH2:3]([O:7][C:9]1[N:14]=[CH:13][N:12]=[C:11]([N:15]2[CH2:21][C@H:20]([CH3:22])[CH2:19][CH2:18][CH2:17][C@@H:16]2[CH3:23])[C:10]=1[F:24])[C:4]#[C:5][CH3:6]

Participants

6

Reactant 4

HCID 129912-Butyn-1-olHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 866074631-(6-chloro-5-fluoropyrimidin-4-yl)-cis-2,6-dimethylhexahydro-1H-azepine

Product 1

HCID 665946871-(6-(2-butynyloxy)-5-fluoropyrimidin-4-yl)-cis-2,6-dimethyl-hexahydro-1H-azepineYield 106.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

0.10 g of sodium hydride (60% oil suspension) was suspended in 3 ml of tetrahydrofuran. 0.5 ml of tetrahydrofuran solution of 0.15 g of 2-butyn-1-ol was added dropwise at room temperature therein, and the mixture was stirred for 10 minutes. Into the mixture was added dropwise 0.5 ml of tetrahydrofuran solution of 0.30 g of 1-(6-chloro-5-fluoropyrimidin-4-yl)-cis-2,6-dimethyl-hexahydro-1H-azepine at room temperature, and stirred for 8 hours at 70° C. After the reaction mixture was cooled to near room temperature, the reaction mixture was poured into 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 0.36 g of 1-(6-(2-butynyloxy)-5-fluoropyrimidin-4-yl)-cis-2,6-dimethyl-hexahydro-1H-azepine (hereinafter, referred to as Compound (41)).

Workup

  1. stirringstirred for 8 hours at 70° C
  2. extractionthe mixture was extracted with tert-butyl methyl ether three times
  3. washThe organic layers were washed with a saturated sodium chloride aqueous solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-35ed7cdee41b482ba2fe92304c403aba
Source dataset
uspto-grants-2011_07
Patent number
US07973028B2

Linked notes

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