N-methyl-2-pyrrolidone → HCID 67451838, compound

HRID 869146Notes

Reaction equation

HRID 869146 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:4][CH:3]=1.[F:12][C:13]1[C:14]([C:19]2([CH2:23][NH2:24])[CH2:22][CH2:21][CH2:20]2)=[N:15][CH:16]=[CH:17][CH:18]=1.CCN(C(C)C)C(C)C.CN1C(=O)CCC1>O.C(OCC)(=O)C>[F:12][C:13]1[C:14]([C:19]2([CH2:23][NH:24][C:2]3[N:7]=[N:6][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:4][CH:3]=3)[CH2:22][CH2:21][CH2:20]2)=[N:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 12379801Methyl 6-chloropyridazine-3-carboxylateHCID 67453361HCID 67453361, compound

Product 1

HCID 67451838HCID 67451838, compoundYield 51.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a 20 dram vial was added methyl 6-chloropyridazine-3-carboxylate (510 mg, 2.7 mmol, 1.0 equiv), (1-(3-fluoropyridin-2-yl)cyclobutyl)methanamine (738 mg, 4 mmol, 1.5 equiv), DIPEA (0.7 mL, 4 mmol, 1.5 equiv), and NMP (2 mL). The reaction was heated at 120° C. for 40 min and then diluted with water (20 mL) and ethyl acetate (50 mL). After transferring to a separatory funnel and shaking, the organic layer was separated from the aqueous layer and then washed with brine (1×20 mL). The organic layer was then dried over Na2SO4, filtered, and concentrated to give a crude solid that was purified by silica gel column chromatography (20-100% EtOAc/hexanes) to give 440 mg (48%) of methyl 6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazine-3-carboxylate as a white solid. m/z=331.1 [M+H]+.

Workup

  1. customAfter transferring to a separatory funnel
  2. customthe organic layer was separated from the aqueous layer
  3. washwashed with brine (1×20 mL)
  4. dry with materialThe organic layer was then dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude solid that
  8. customwas purified by silica gel column chromatography (20-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-9aefe431a2394a08ad4021e56a9e60a6
Source dataset
uspto-grants-2015_03
Patent number
US08969346B2

Reaction notes

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