1-Methylpyrrolidine → 1-(2-Fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)-3-(2-(1-(trifluoromethyl)cyclopropyl)ethyl)urea

HRID 522740Notes

Reaction equation

HRID 522740 reaction equation
C=C([O:4][C:5](=O)[NH:6][C:7]1[CH:12]=[C:11]([C:13]2[C:24]([CH3:25])=[N:23][C:16]3[N:17]=[C:18]([NH:21][CH3:22])[N:19]=[CH:20][C:15]=3[CH:14]=2)[C:10]([CH3:26])=[CH:9][C:8]=1[F:27])C.Cl.[F:30][C:31]([F:39])([F:38])[C:32]1([CH2:35][CH2:36][NH2:37])[CH2:34][CH2:33]1.CN1CCCC1>C1COCC1.CCOC(C)=O>[F:27][C:8]1[CH:9]=[C:10]([CH3:26])[C:11]([C:13]2[C:24]([CH3:25])=[N:23][C:16]3[N:17]=[C:18]([NH:21][CH3:22])[N:19]=[CH:20][C:15]=3[CH:14]=2)=[CH:12][C:7]=1[NH:6][C:5]([NH:37][CH2:36][CH2:35][C:32]1([C:31]([F:39])([F:38])[F:30])[CH2:34][CH2:33]1)=[O:4]

Participants

6

Reactant 3

HCID 84541-MethylpyrrolidineHCID 898137322-(1-(Trifluoromethyl)cyclopropyl)ethan-1-amine hydrochlorideHCID 118048014Prop-1-en-2-yl (2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)carbamate

Product 1

HCID 1180361121-(2-Fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)-3-(2-(1-(trifluoromethyl)cyclopropyl)ethyl)ureaYield 42%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

Treat a mixture of prop-1-en-2-yl(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)carbamate (1.09 g, 2.86 mmol) and 2-(1-(trifluoromethyl)cyclopropyl)ethanamine hydrochloride (0.542 g, 2.86 mmol) in THF (30 mL) with 1-methylpyrrolidine (1.52 mL, 14.3 mmol) and heat at 65° C. for 4 h. Cool the mixture to RT, dilute with EtOAc, wash with brine (2×), dry over MgSO4, concentrate to dryness and purify via silica gel chromatography (MeOH/EtOAc). Treat the resulting material with acetonitrile, cool to −20° C. for 2 h, collect the solids via filtration, rinse with acetonittrile (−20° C.) and dry to afford the title compound as a pale yellow solid (570 mg, 42% yield). MS (m/z): 477.2 (M+1).

Workup

  1. additionTreat
  2. temperatureCool the mixture to RT
  3. washwash with brine (2×)
  4. dry with materialdry over MgSO4
  5. concentrationconcentrate to dryness
  6. custompurify via silica gel chromatography (MeOH/EtOAc)
  7. additionTreat the resulting material with acetonitrile
  8. temperaturecool to −20° C. for 2 h
  9. customcollect the solids
  10. filtrationvia filtration
  11. washrinse with acetonittrile (−20° C.)
  12. customdry

Sources & evidence

ORD record
ord-fa11ad1318584180aaddf951cb720a11
Source dataset
uspto-grants-2016_05
Patent number
US09334267B2

Reaction notes

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