Hydrochloric Acid → HCID 66666457, compound

HRID 2276528Notes

Reaction equation

HRID 2276528 reaction equation
[C:1]1([C:7]2[N:12]=[C:11]3[CH2:13][CH2:14][CH2:15][N:16]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([O:25]CC)=[O:24])[C:10]3=[N:9][C:8]=2[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.[OH-].[Li+].Cl>C1COCC1.CO.O>[C:1]1([C:7]2[N:12]=[C:11]3[CH2:13][CH2:14][CH2:15][N:16]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])[C:10]3=[N:9][C:8]=2[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 66665832HCID 66665832, compound

Product 1

HCID 66666457HCID 66666457, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 7-(2,3-diphenyl-7,8-dihydropyrido[3,2-b]pyrazin-5(6H)-yl)heptanoate (step 2)(6.1 g, 13.8 mmol) in THF (300 ml) and MeOH (100 ml) was treated with a solution of lithium hydroxide monohydrate (3.5 g, 83 mmol) in water (100 ml). The reaction mixture was heated at reflux for 5 h and allowed to cool to room temperature. The pH of the mixture was adjusted to <pH5 using 2M HCl. The volatile solvents were removed in vacuo and the remaining residue was diluted with water (50 ml) and extracted with EtOAc (3×). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to yield a greenish grey solid. The crude material was dissolved in MeOH (30 ml) and purified in 2 portions on a cartridge packed with 113 g LiChroprep® RP-18 (40-63 μm, supplier Merck, reverse phase column) eluting with 10-100% MeCN in water. The resulting solid was re-crystallized from a hot mixture of EtOH (120 ml) and water (90 ml). After seeding and stirring for 1 h at 5° C., the crystals were filtered off and the product dried for 2 days at 40° C. in a vacuum oven to afford the title compound;

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 5 h
  3. customThe volatile solvents were removed in vacuo
  4. additionthe remaining residue was diluted with water (50 ml)
  5. extractionextracted with EtOAc (3×)
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto yield a greenish grey solid
  11. custompurified in 2 portions on a cartridge
  12. washeluting with 10-100% MeCN in water
  13. customThe resulting solid was re-crystallized from a hot mixture of EtOH (120 ml) and water (90 ml)
  14. filtrationthe crystals were filtered off
  15. customthe product dried for 2 days at 40° C. in a vacuum oven

Sources & evidence

ORD record
ord-bd9d2556861548bebd228b2e47fd21b9
Source dataset
uspto-grants-2015_09
Patent number
US09132127B2

Reaction notes

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