1-Methylpyrrolidine → HCID 89813798, compound

HRID 522745Notes

Reaction equation

HRID 522745 reaction equation
[CH3:1][C:2]([CH3:13])([CH3:12])[CH2:3][CH2:4][NH:5][C:6](=[O:11])OC(C)=C.[NH2:14][C:15]1[C:16]([F:34])=[CH:17][C:18]([F:33])=[C:19]([C:21]2[CH:32]=[N:31][C:24]3[N:25]=[C:26]([NH:29][CH3:30])[N:27]=[CH:28][C:23]=3[CH:22]=2)[CH:20]=1.CN1CCCC1.C1CCN2C(=NCCC2)CC1>O1CCOCC1>[F:34][C:16]1[CH:17]=[C:18]([F:33])[C:19]([C:21]2[CH:32]=[N:31][C:24]3[N:25]=[C:26]([NH:29][CH3:30])[N:27]=[CH:28][C:23]=3[CH:22]=2)=[CH:20][C:15]=1[NH:14][C:6]([NH:5][CH2:4][CH2:3][C:2]([CH3:1])([CH3:12])[CH3:13])=[O:11]

Participants

6

Reactant 4

HCID 84541-MethylpyrrolidineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 89813400HCID 89813400, compoundHCID 101043215HCID 101043215, compound

Product 1

HCID 89813798HCID 89813798, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

Treat a solution of prop-1-en-2-yl (3,3-dimethylbutyl)carbamate (0.039 g, 0.209 mmol) and 6-(5-amino-2,4-difluorophenyl)-N-methylpyrido[2,3-d]pyrimidin-2-amine (0.060 g, 0.209 mmol) in dioxane (5 mL) with catalytic 1-methylpyrrolidine (1.8 mg, 0.021 mmol) and heat at 65° C. overnight. Add 2,3,4,6,7,8,9,10-Octahydropyrimidol[1,2-a]azepine (0.1 mL) and additional prop-1-en-2-yl (3,3-dimethylbutyl) (25 mg, 0.135 mmol) and heat the mixture at 85° C. overnight. Add additional 2,3,4,6,7,8,9,10-Octahydropyrimidol[1,2-a]azepine (0.1 mL) and prop-1-en-2-yl (3,3-dimethylbutyl) (25 mg, 0.135 mmol) and heat the mixture at 85° C. for another 24 h. Cool the mixture to RT, concentrate to dryness and purify via silica gel chromatography (EtOAc/Hexane). Treat the resulting material with DCM, allow to stand at RT overnight, and collect the solid via filtration to afford 1-(2,4-difluoro-5-(2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)-3-(3,3-dimethylbutyl)urea (30 mg, 35% yield). MS (m/z): 415.2 (M+1).

Workup

  1. temperatureheat the mixture at 85° C. for another 24 h
  2. temperatureCool the mixture to RT
  3. concentrationconcentrate to dryness
  4. custompurify via silica gel chromatography (EtOAc/Hexane)
  5. additionTreat the resulting material with DCM
  6. customcollect the solid
  7. filtrationvia filtration

Sources & evidence

ORD record
ord-28019680843c457ca0fe3a69aa2d422a
Source dataset
uspto-grants-2016_05
Patent number
US09334267B2

Reaction notes

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