Ammonium Chloride → Ethyl 2-[6-(4,4-dimethylcyclohexyl)-2-methylthieno[2,3-d]pyrimidin-4-yl]-3-(1,1-dioxidothiomorpholin-4-yl)-3-oxopropanoate

HRID 2171798Notes

Reaction equation

HRID 2171798 reaction equation
[O:1]=[S:2]1(=[O:16])[CH2:7][CH2:6][N:5]([C:8](=[O:15])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:4][CH2:3]1.Cl[C:18]1[C:19]2[CH:27]=[C:26]([CH:28]3[CH2:33][CH2:32][C:31]([CH3:35])([CH3:34])[CH2:30][CH2:29]3)[S:25][C:20]=2[N:21]=[C:22]([CH3:24])[N:23]=1.[NH4+].[Cl-]>COCCOC>[CH3:34][C:31]1([CH3:35])[CH2:32][CH2:33][CH:28]([C:26]2[S:25][C:20]3[N:21]=[C:22]([CH3:24])[N:23]=[C:18]([CH:9]([C:8]([N:5]4[CH2:6][CH2:7][S:2](=[O:1])(=[O:16])[CH2:3][CH2:4]4)=[O:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:19]=3[CH:27]=2)[CH2:29][CH2:30]1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 118023222Ethyl 3-(1,1-dioxidothiomorpholin-4-yl)-3-oxopropanoateHCID 1180235544-Chloro-6-(4,4-dimethylcyclohexyl)-2-methylthieno[2,3-d]pyrimidine

Product 1

HCID 118023708Ethyl 2-[6-(4,4-dimethylcyclohexyl)-2-methylthieno[2,3-d]pyrimidin-4-yl]-3-(1,1-dioxidothiomorpholin-4-yl)-3-oxopropanoateYield 43.3%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

Under an argon atmosphere, to DME (12.5 mL) that had been ice-cooled was added Nall (60% oil, 203 mg), followed by stirring for 10 minutes. To this mixture was added dropwise a solution of ethyl 3-(1,1-dioxidothiomorpholin-4-yl)-3-oxopropanoate (1.40 g) in DME (10 mL), followed by stirring at the same temperature for 30 minutes. Then, 4-chloro-6-(4,4-dimethylcyclohexyl)-2-methylthieno[2,3-d]pyrimidine (750 mg) was added thereto, followed by stirring at 60° C. overnight. The reaction mixture was left to be cooled, and then a saturated aqueous NH4Cl solution was added thereto, followed by extraction with EtOAc. The organic layer was washed sequentially with water and brine, dried over MgSO4, and then concentrated under reduced pressure. The residue was purified by silica gel column to obtain ethyl 2-[6-(4,4-dimethylcyclohexyl)-2-methylthieno[2,3-d]pyrimidin-4-yl]-3-(1,1-dioxidothiomorpholin-4-yl)-3-oxopropanoate (559 mg).

Workup

  1. temperaturecooled
  2. stirringby stirring at the same temperature for 30 minutes
  3. stirringby stirring at 60° C. overnight
  4. waitThe reaction mixture was left
  5. temperatureto be cooled
  6. extractionfollowed by extraction with EtOAc
  7. washThe organic layer was washed sequentially with water and brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column

Sources & evidence

ORD record
ord-2e170361f7d340078344772c925e6114
Source dataset
uspto-grants-2015_06
Patent number
US09051339B2

Reaction notes

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