Potassium Carbonate → HCID 68379922, compound

HRID 2364958Notes

Reaction equation

HRID 2364958 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[C:17](=[O:18])[N:11]3[CH2:12][CH2:13][NH:14][C:15](=[O:16])[C:10]3=[CH:9][CH:8]=2)[CH:6]=1.C(=O)([O-])[O-].[K+].[K+].Cl.CC1N=CN(C2C(=O)NC(C(O)=O)=CC=2)C=1.Cl.[Cl:43][CH2:44][CH2:45]NCCCl.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C)C=O.O>[Cl:43][CH2:44][CH2:45][N:14]1[CH2:13][CH2:12][N:11]2[C:17](=[O:18])[C:7]([N:5]3[CH:6]=[C:2]([CH3:1])[N:3]=[CH:4]3)=[CH:8][CH:9]=[C:10]2[C:15]1=[O:16]

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 522769Bis(2-chloroethyl)amine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68380187HCID 68380187, compoundHCID 86762326HCID 86762326, compound

Product 1

HCID 68379922HCID 68379922, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Synthesis of 242-chloroethyl)-7-(4-methyl-1H-imidazol-1-yl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione (P2). Potassium carbonate (195.4 g, 1414 mmol) was added to a mixture of 5-(4-methyl-1H-imidazol-1-yl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid, hydrochloride salt (C3) (34.5 g, 135 mmol) and 2-chloro-N-(2-chloroethyl)ethanamine hydrochloride (37.8 g, 212 mmol) in N,N-dimethylformamide (670 mL), and the reaction was stirred for 10 minutes. O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 83.5 g, 219 mmol) was added and stirring was continued for an additional 3 hours and 40 minutes. The reaction mixture was then poured into water (4 L) and stirred for 30 minutes. After extraction with dichloromethane (3×1 L), the combined organic layers were washed with saturated aqueous sodium chloride solution (3×3 L), dried over magnesium sulfate, filtered and concentrated in vacuo. Finally, most of the DMF was removed by using a methanol/liquid nitrogen cooler. The residue was stirred in ethyl acetate (approximately 50 mL) for 30 minutes. The solids were collected by filtration and washed with ethyl acetate and pentane, providing the title compound as a yellow solid. Yield: 23.0 g, 75.0 mmol, 56%. LCMS m/z 307.1 (M+1). 1H-NMR (300 MHz, CDCl3) δ 2.29 (br s, 3H), 3.80-3.93 (m, 6H), 4.38-4.44 (m, 2H), 7.13-7.16 (m, 1H), 7.27 (d, J=7.6 Hz, 1H), 7.45 (d, J=7.6 Hz, 1H), 8.24 (d, J=1.0 Hz, 1H).

Workup

  1. stirringstirring
  2. waitwas continued for an additional 3 hours and 40 minutes
  3. stirringstirred for 30 minutes
  4. extractionAfter extraction with dichloromethane (3×1 L)
  5. washthe combined organic layers were washed with saturated aqueous sodium chloride solution (3×3 L)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customFinally, most of the DMF was removed
  10. stirringThe residue was stirred in ethyl acetate (approximately 50 mL) for 30 minutes
  11. filtrationThe solids were collected by filtration
  12. washwashed with ethyl acetate and pentane

Sources & evidence

ORD record
ord-600d3dc906fc4349a06908574c8496fa
Source dataset
uspto-grants-2014_04
Patent number
US08697673B2

Reaction notes

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