Pyridine → N-(6-(7-azabicyclo[2.2.1]heptan-7-yl)-4-methylpyridin-3-yl)-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

HRID 869500Notes

Reaction equation

HRID 869500 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:15])[C:5]([C:12]([OH:14])=O)=[CH:6][NH:7]2.[CH:16]12[N:22]([C:23]3[N:28]=[CH:27][C:26]([NH2:29])=[C:25]([CH3:30])[CH:24]=3)[CH:19]([CH2:20][CH2:21]1)[CH2:18][CH2:17]2.N1C=CC=CC=1>CC1CCCO1.C(OCC)(=O)C>[CH:16]12[N:22]([C:23]3[N:28]=[CH:27][C:26]([NH:29][C:12]([C:5]4[C:4](=[O:15])[C:3]5[C:8](=[CH:9][CH:10]=[CH:11][C:2]=5[CH3:1])[NH:7][CH:6]=4)=[O:14])=[C:25]([CH3:30])[CH:24]=3)[CH:19]([CH2:20][CH2:21]1)[CH2:18][CH2:17]2

Participants

6

Reactant 3

HCID 1049PyridineHCID 156185565-Methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acidHCID 593162336-(7-Azabicyclo[2.2.1]heptan-7-yl)-4-methylpyridin-3-amine

Product 1

HCID 45259022N-(6-(7-azabicyclo[2.2.1]heptan-7-yl)-4-methylpyridin-3-yl)-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxamideYield 26.2%

Reagents, catalysts & solvents 2

HCID 73012-MethyltetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-methyl-4-oxo-1H-quinoline-3-carboxylic acid (60 mg, 0.2953 mmol) and 6-(7-azabicyclo[2.2.1]heptan-7-yl)-4-methyl-pyridin-3-amine (60.03 mg, 0.2953 mmol) in 2-methyltetrahydrofuran (1 mL) was added propyl phosphonic acid cyclic anhydride (375.8 μL of 50% w/v, 0.5906 mmol) followed by pyridine (46.72 mg, 47.77 μL, 0.5906 mmol). The mixture was irradiated under microwave conditions for 1 h at 100° C. The crude reaction mixture was diluted with ethyl acetate (2 mL) and quenched with 10% NaHCO3 solution (3 mL). The resulting precipitate was filtered and washed with ethyl acetate (5 mL). The solid was resuspended in 20% aqueous Na2CO3 (5 mL)/methanol (2 mL) and stirred for 30 min. The solid was filtered, rinsed with water and air dried to provide N-(6-(7-azabicyclo[2.2.1]heptan-7-yl)-4-methylpyridin-3-yl)-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxamide (30 mg, 26% yield). LC/MS m/z 389.4 [M+H]+, retention time 1.33 min (RP—C18, 10-99% CH3CN/0.05% TFA over 3 min).

Workup

  1. customThe mixture was irradiated under microwave conditions for 1 h at 100° C
  2. customThe crude reaction mixture
  3. customquenched with 10% NaHCO3 solution (3 mL)
  4. filtrationThe resulting precipitate was filtered
  5. washwashed with ethyl acetate (5 mL)
  6. filtrationThe solid was filtered
  7. washrinsed with water and air
  8. customdried

Sources & evidence

ORD record
ord-93ca6d904b39435aabbff3814b97f99e
Source dataset
uspto-grants-2015_03
Patent number
US08969382B2

Reaction notes

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