4-Methylmorpholine → HCID 9799980, compound

HRID 353932Notes

Reaction equation

HRID 353932 reaction equation
Cl.Cl.[C:3]([C:5]1([NH:12][C:13]([CH:15]([NH2:21])[CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:14])[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]1)#[N:4].CN1CCOCC1.[N:29]1([C:35](Cl)=[O:36])[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1>CN(C=O)C>[C:3]([C:5]1([NH:12][C:13]([CH:15]([NH:21][C:35]([N:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)=[O:36])[CH2:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:14])[CH2:6][CH2:7][N:8]([CH3:11])[CH2:9][CH2:10]1)#[N:4]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 848104-Morpholinecarbonyl chlorideHCID 69662894HCID 69662894, compound

Product 1

HCID 9799980HCID 9799980, compoundYield 21.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

[1-(4-cyano-1-methyl-piperidin-4-ylcarbamoyl)-3,3-dimethyl-butyl]-amine dihydrochloride (350 mg, 1.03 mmol) was mixed in 10 mL of DMF to which was added 1 mL of N-methyl morpholine followed by addition of 4-morpholine carbonyl chloride (180 mg, 1.20 mmol) as a solution in 5 mL of DMF. The reaction was stirred for 16 hours at which time the volatiles were removed in vacuo. The residue was redissolved in 150 mL of EtOAc and washed sequentially with 50 mL of saturated aqueous bicarbonate and 50 mL of brine. The organic layer was dried over sodium sulfate, decanted and concentrated. The product was purified by flash chromatography on silica gel using 100% methylene chloride to 12% methanol in methylene chloride as eluent to give the title compound as a thick oil (85 mg); MS, m/z 380=M+1.

Workup

  1. customwere removed in vacuo
  2. dissolutionThe residue was redissolved in 150 mL of EtOAc
  3. washwashed sequentially with 50 mL of saturated aqueous bicarbonate and 50 mL of brine
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customdecanted
  6. concentrationconcentrated
  7. customThe product was purified by flash chromatography on silica gel using 100% methylene chloride to 12% methanol in methylene chloride as eluent

Sources & evidence

ORD record
ord-24e223ce4aa04494ae635d836c355d33
Source dataset
uspto-grants-2004_06
Patent number
US06756372B2

Reaction notes

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