Triethylamine → cis-(1-(4-Amino-5-nitropyrimidin-2-yl)-4-methylpiperidin-3-yl)(pyrrolidin-1-yl)methanone

HRID 931306Notes

Reaction equation

HRID 931306 reaction equation
[CH3:1][C@H:2]1[CH2:7][CH2:6][NH:5][CH2:4][C@H:3]1[C:8]([N:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1)=[O:9].C(N(CC)CC)C.Cl[C:23]1[N:28]=[C:27]([NH2:29])[C:26]([N+:30]([O-:32])=[O:31])=[CH:25][N:24]=1>C(#N)C>[NH2:29][C:27]1[C:26]([N+:30]([O-:32])=[O:31])=[CH:25][N:24]=[C:23]([N:5]2[CH2:6][CH2:7][C@H:2]([CH3:1])[C@H:3]([C:8]([N:10]3[CH2:14][CH2:13][CH2:12][CH2:11]3)=[O:9])[CH2:4]2)[N:28]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 747162-Chloro-5-nitropyrimidin-4-amineHCID 89853245cis-(4-Methylpiperidin-3-yl)(pyrrolidin-1-yl)methanone

Product 1

HCID 89853969cis-(1-(4-Amino-5-nitropyrimidin-2-yl)-4-methylpiperidin-3-yl)(pyrrolidin-1-yl)methanoneYield 69.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of cis-(4-methylpiperidin-3-yl)(pyrrolidin-1-yl)methanone (1.7 g, 8.60 mmol) in acetonitrile (20 mL) was added triethylamine (3.65 mL, 26.02 mmol). The mixture was stirred for 10 min at room temperature. Then 2-chloro-5-nitropyrimidin-4-amine (1.19 g, 6.9 mmol) was added and the reaction mixture was stirred at 80° C. for 3 h. The mixture was cooled to room temperature and stirred for 1 h. Ice cold water was added and the mixture was extracted with ethyl acetate. The organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified via column chromatography (40-100% ethyl acetate in petroleum ether) to afford cis-(1-(4-amino-5-nitropyrimidin-2-yl)-4-methylpiperidin-3-yl)(pyrrolidin-1-yl)methanone (1.6 g). MS (ES+) (M+H) 335.3.

Workup

  1. stirringthe reaction mixture was stirred at 80° C. for 3 h
  2. temperatureThe mixture was cooled to room temperature
  3. stirringstirred for 1 h
  4. additionIce cold water was added
  5. extractionthe mixture was extracted with ethyl acetate
  6. dry with materialThe organics were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified via column chromatography (40-100% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-65077782a85b4e0d9bf598abb56b15f1
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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