1-Methylpyrrolidine → HCID 86702112, compound

HRID 873599Notes

Reaction equation

HRID 873599 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:11][CH:10]([C:12]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([C:21]4[CH:22]=[N:23][N:24]([CH2:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH:25]=4)=[CH:17][CH:16]=3)=[O:13])[CH2:9]2)=[CH:4][CH:3]=1.[Cl-].C[Zn+].[CH3:34]N1CCCC1>[Pd].ClCCl>[CH3:28][C:27]([CH3:30])([CH3:29])[CH2:26][N:24]1[CH:25]=[C:21]([C:18]2[CH:19]=[CH:20][C:15]([NH:14][C:12]([CH:10]3[CH2:11][N:8]([C:5]4[N:6]=[N:7][C:2]([CH3:34])=[CH:3][CH:4]=4)[CH2:9]3)=[O:13])=[CH:16][CH:17]=2)[CH:22]=[N:23]1

Participants

6

Reactant 3

HCID 84541-MethylpyrrolidineHCID 86702113HCID 86702113, compoundHCID 178477797HCID 178477797, compound

Product 1

HCID 86702112HCID 86702112, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To 1-(6-chloropyridazin-3-yl)-N-(4-(1-neopentyl-1H-pyrazol-4-yl)phenyl)azetidine-3-carboxamide (0.076 g, 0.179 mmol) was added methylzinc(II) chloride (2.0M in THF) (0.179 ml, 0.358 mmol) and 5 mg of palladium catalyst. The reaction mixture was heated to 60° C. and a thick precipitate developed. N-methylpyrrolidine (0.2 ml) was added and the mixture was heated to 85° C. for 2 hours. The mixture was diluted with dichloromethane and purified by normal phase chromatography to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.11 (s, 1H), 8.04 (s, 1H), 7.82 (s, 1H), 7.61 (d, J=8.7 Hz, 2H), 7.53 (d, J=8.7 Hz, 2H), 7.43 (d, J=9.2 Hz, 1H), 6.99 (d, J=9.1 Hz, 1H), 4.27 (t, J=8.5 Hz, 2H), 4.19 (dd, J=8.2, 6.1 Hz, 2H), 3.90 (s, 2H), 3.75 (ddd, J=17.0, 8.5, 6.0 Hz, 1H), 2.45 (s, 3 H), 0.92 (s, 9 H); MS (ESI(+)) m/e 405 (M+H)+.

Workup

  1. temperaturethe mixture was heated to 85° C. for 2 hours
  2. custompurified by normal phase chromatography

Sources & evidence

ORD record
ord-725a3034235c4fecb91a1bc6c34ea66c
Source dataset
uspto-grants-2015_03
Patent number
US08975398B2

Reaction notes

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