Dimethylformamide → HCID 89567430, compound

HRID 1477362Notes

Reaction equation

HRID 1477362 reaction equation
[CH3:1][N:2](C=O)C.[H-].[Na+].[Cl:8][C:9]1[CH:14]=[C:13]([NH:15][CH3:16])[C:12]([C:17]2[CH:18]=[N:19][N:20]([CH3:22])[CH:21]=2)=[CH:11][N:10]=1.IC>C([O-])(O)=O.[Na+].C(OCC)(=O)C.C(Cl)Cl>[NH3:2].[Cl:8][C:9]1[CH:14]=[C:13]([N:15]([CH3:1])[CH3:16])[C:12]([C:17]2[CH:18]=[N:19][N:20]([CH3:22])[CH:21]=2)=[CH:11][N:10]=1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 71512252HCID 71512252, compound

Product 2

HCID 222AmmoniaYield 1%HCID 89567430HCID 89567430, compoundYield 92%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
80 °C

Procedure

DMF (2.99 mL) was slowly added to stirred sodium hydride (60% in oil; 51 mg, 1.28 mmol) and 2-chloro-N-methyl-5-(1-methyl-1H-pyrazol-4-yl)pyridin-4-amine (Intermediate I-15) (104 mg, 0.467 mmol) at room temperature. The mixture was warmed to 80° C. for 10 minutes, followed by addition of iodomethane (0.035 mL, 0.560 mmol). The mixture was stirred at 80° C. for 30 minutes, then cooled and diluted with saturated aqueous NaHCO3 (45 mL) and ethyl acetate (70 mL). After stirring for 10 minutes, the organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×70 mL). The combined organic layers were evaporated onto silica gel. Gradient chromatography, eluting with 1-10% MeOH: 1% NH3 in CH2Cl2 over 10 column volume, gave 2-chloro-N,N-dimethyl-5-(1-methyl-1H-pyrazol-4-yl)pyridin-4-amine (102 mg, 0.431 mmol, 92% yield).

Workup

  1. temperaturecooled
  2. stirringAfter stirring for 10 minutes
  3. customthe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (2×70 mL)
  5. customThe combined organic layers were evaporated onto silica gel
  6. washGradient chromatography, eluting with 1-10% MeOH

Sources & evidence

ORD record
ord-b0422a14eceb48e285eafb50e944692e
Source dataset
uspto-grants-2016_08
Patent number
US09403797B2

Reaction notes

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