1-Methylpyrrolidine → HCID 71737335, compound

HRID 715133Notes

Reaction equation

HRID 715133 reaction equation
C=C([O:4][C:5](=O)[NH:6][C:7]1[CH:12]=[C:11]([C:13]2[C:14]([CH3:25])=[N:15][C:16]3[C:21]([CH:22]=2)=[CH:20][N:19]=[C:18]([NH:23][CH3:24])[CH:17]=3)[C:10]([CH3:26])=[CH:9][C:8]=1[F:27])C.C(O)(=O)C.C(O)(=O)C.[F:37][C:38]([CH3:43])([CH3:42])[CH2:39][CH2:40][NH2:41].CN1CCCC1>C1COCC1>[F:37][C:38]([CH3:43])([CH3:42])[CH2:39][CH2:40][NH:41][C:5]([NH:6][C:7]1[CH:12]=[C:11]([C:13]2[C:14]([CH3:25])=[N:15][C:16]3[C:21]([CH:22]=2)=[CH:20][N:19]=[C:18]([NH:23][CH3:24])[CH:17]=3)[C:10]([CH3:26])=[CH:9][C:8]=1[F:27])=[O:4]

Participants

5

Reactant 3

HCID 84541-MethylpyrrolidineHCID 89827693HCID 89827693, compoundHCID 131734085HCID 131734085, compound

Product 1

HCID 71737335HCID 71737335, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Combine prop-1-en-2-yl(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)carbamate (2.5 g, 6.6 mmol), 3-fluoro-3-methylbutan-1-amine diacetate (1.8 g, 7.9 mmol), and N-methylpyrrolidine (2.7 mL, 26.0 mmole) in THF (50 mL) and heat at 50° C. overnight. Evaporate under reduced pressure and partition between NaHCO3 and EtOAc. Wash the organic layer with brine, dry over Na2SO4, concentrate in vacuo, and purify by silica gel chromatography (50-100% EtOAc/DCM) to obtain the title compound (2.0 g, 71%). 1H NMR (400 MHz, DMSO-d6): δ 8.82 (s, 1H), 8.33 (s, 1H), 7.93 (d, J=8 Hz, 1H), 7.83 (s, 1H), 7.16 (d, J=8 Hz, 1H), 6.73 (m, 1H), 6.56 (m, 1H), 6.52 (s, 1H), 3.15 (m, 2H), 2.82 (d, J=5 Hz, 3H), 2.27 (s, 3H), 1.94 (s, 3H), 1.73 (m, 2H), 1.30 (d, J=21.6 Hz, 6H); MS (ESI) m/z: 428.2 (M+H+).

Workup

  1. customEvaporate under reduced pressure
  2. custompartition between NaHCO3 and EtOAc
  3. washWash the organic layer with brine
  4. dry with materialdry over Na2SO4
  5. concentrationconcentrate in vacuo
  6. custompurify by silica gel chromatography (50-100% EtOAc/DCM)

Sources & evidence

ORD record
ord-a739abddb5ba49d38a59b419c97dccb4
Source dataset
uspto-grants-2015_11
Patent number
US09187474B2

Reaction notes

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