7-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid → HCID 59598351, compound

HRID 2359715Notes

Reaction equation

HRID 2359715 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH2:21])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:19][CH3:20])=[CH:16][CH:17]=2)[N:12]=[CH:11][CH:10]=1.[CH3:22][C:23]1[CH:24]=[CH:25][C:26]2[N:27]([CH:36]=1)[C:28](=[O:35])[C:29]([C:32](O)=[O:33])=[CH:30][N:31]=2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl.C([O-])(O)=O.[Na+]>[F:1][C:2]1[CH:3]=[C:4]([NH:21][C:32]([C:29]2[C:28](=[O:35])[N:27]3[CH:36]=[C:23]([CH3:22])[CH:24]=[CH:25][C:26]3=[N:31][CH:30]=2)=[O:33])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:19][CH3:20])=[CH:16][CH:17]=2)[N:12]=[CH:11][CH:10]=1

Participants

6

Reactant 3

HCID 87681627-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595983543-Fluoro-4-(7-methoxyquinolin-4-yloxy)benzenamine

Product 1

HCID 59598351HCID 59598351, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a suspension of ethyl 7-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylate (0.11 g, 0.47 mmol) in ethanol was added 1 N NaOH solution (3 mL, 3 mmol) at RT. The reaction mixture was stirred for 16 at RT. The resultant was concentrated, and the residue was diluted with water. The aqueous solution was washed with diethyl ether and then acidified with 2N HCl solution and extracted with dichloromethane. The organic solution was dried over magnesium sulfate and concentrated to give a yellow solid (0.090 g, 93%): MS (ESI pos. ion) m/z: 205 (MH+). Calc'd exact mass for C10H8N2O3: 204. A mixture of 3-fluoro-4-(7-methoxyquinolin-4-yloxy)benzenamine (0.08 g, 0.3 mmol), 7-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid (0.08 g, 0.4 mmol), HATU (0.4 g, 0.8 mmol) in dichlormethane was stirred for 16 h. Then, the mixture was diluted with dichloromethane and aq. NaHCO3 solution. The organic layer was separated, dried over Na2SO4 and concentrated. The residue was purified by ISCO (0-5% MeOH in EtOAc) to give the title compound as a yellow solid (0.032 g, 24%): MS (ESI pos. ion) m/z: 471 (MH+), Calc'd exact mass for C26H19FN4O4: 470; 1HNMR (400 MHz, CDCl3): 11.4 (s, 1H), 9.4 (s, 1H), 9.1 (s, 1H), 8.6 (d, J=6 Hz, 1H), 8.3 (d, J=9 Hz, 1H), 8.0 (dd, J=3, 12 Hz, 1H), 7.9 (m, 2H), 7.5 (m, 1H), 7.4 (d, J=3 Hz, 1H), 7.0-7.3 (m, 2H), 6.4 (d, J=3 Hz, 1H), 3.98 (s, 3H), 2.57 (s, 3H).

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified by ISCO (0-5% MeOH in EtOAc)

Sources & evidence

ORD record
ord-0a83aaa8cba54163bd578910d023106a
Source dataset
uspto-grants-2014_04
Patent number
US08685983B2

Reaction notes

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