Morpholine → N-(5-Methyl-1H-pyrazol-3-yl)-2-(methylthio)-6-morpholin-4-yl-5-nitropyrimidin-4-amine

HRID 450392

Reaction equation

HRID 450392 reaction equation
Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6](Cl)[N:5]=[C:4]([S:12][CH3:13])[N:3]=1.[CH3:14][C:15]1[NH:19][N:18]=[C:17]([NH2:20])[CH:16]=1.CCN(C(C)C)C(C)C.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>C1COCC1.O.CCOC(C)=O>[CH3:14][C:15]1[NH:19][N:18]=[C:17]([NH:20][C:2]2[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[N:5]=[C:4]([S:12][CH3:13])[N:3]=2)[CH:16]=1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 113454584,6-Dichloro-2-(methylthio)-5-nitropyrimidine2×

Product 1

HCID 68734536N-(5-Methyl-1H-pyrazol-3-yl)-2-(methylthio)-6-morpholin-4-yl-5-nitropyrimidin-4-amine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4,6-dichloro-2-(methylthio)-5-nitropyrimidine (Intermediate 56, 820 mg) in THF at 0° C. were added 5-methyl-1H-pyrazol-3-amine (350 mg) and DIPEA (1.6 ml) drop-wise. The resulting mixture was stirred at this temperature for 3 hours whereupon morpholine (1 ml) was added. The resulting mixture was allowed to warm to ambient temperature over 10 hours. The mixture was diluted with H2O and EtOAc and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, saturated NaHCO3 (aq) solution, dried and evaporation of the volatiles under reduced pressure gave a colored residue. Purification by column chromatography (50% EtOAc/hexanes) gave the title compound (820 mg). LCMS: 352 [M+1].

Workup

  1. additionwas added
  2. extractionthe aqueous layer was extracted with EtOAc
  3. washThe combined organic layers were washed with brine, saturated NaHCO3 (aq) solution
  4. customdried
  5. customevaporation of the volatiles under reduced pressure
  6. customgave a colored residue
  7. customPurification by column chromatography (50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-0e93f9d296b14d52880e09c304f1e6b5
Source dataset
uspto-grants-2013_07
Patent number
US08486966B2

Linked notes

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