Formaldehyde → HCID 71765153, compound

HRID 2272986Notes

Reaction equation

HRID 2272986 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[NH:14][C:15](=[O:22])[C:16]4[N:17]([CH:19]=[CH:20][CH:21]=4)[CH:18]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.C=O.[C:25]([BH3-])#N.[Na+].C([O-])(O)=O.[Na+]>C(#N)C.O>[CH3:25][N:1]1[CH2:2][CH2:3][CH:4]([C:7]2[CH:8]=[CH:9][C:10]([C:13]3[NH:14][C:15](=[O:22])[C:16]4[N:17]([CH:19]=[CH:20][CH:21]=4)[CH:18]=3)=[CH:11][CH:12]=2)[CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 71765148HCID 71765148, compound

Product 1

HCID 71765153HCID 71765153, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

3-(4-Piperidin-4-yl-phenyl)-2H-pyrrolo[1,2-a]pyrazin-1-one (50.0 mg; 0.17 mmol) is dissolved in acetonitrile (1.5 mL), 35% aqueous formaldehyde solution (67.0 μl; 0.84 mmol) is added and the reaction mixture is stirred for 5 min. Sodium cyanoborohydride (21.2 mg; 0.34 mmol) is added in small portions and the reaction stirred for 2 h. The reaction mixture is diluted with water, treated with saturated NaHCO3 solution and extracted with ethylacetate (three times). The combined organic layers are washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The crude product is purified by preparative HPLC. The combined fractions are concentrated in vacuo, the aqueous residue is made basic with saturated NaHCO3 solution, treated with NaCl (solid) and extracted with ethylacetate (four times). The combined organic layers are washed with brine, dried over Na2SO4, filtered off by suction and evaporated to dryness to afford 3-[4-(1-methyl-piperidin-4-yl)-phenyl]-2H-pyrrolo[1,2-a]pyrazin-1-one as beige solid; HPLC/MS 1.28 min (A), [M+H] 308;

Workup

  1. stirringthe reaction stirred for 2 h
  2. extractionextracted with ethylacetate (three times)
  3. washThe combined organic layers are washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe crude product is purified by preparative HPLC
  8. concentrationThe combined fractions are concentrated in vacuo
  9. additiontreated with NaCl (solid)
  10. extractionextracted with ethylacetate (four times)
  11. washThe combined organic layers are washed with brine
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered off by suction
  14. customevaporated to dryness

Sources & evidence

ORD record
ord-e41ef95f58ee4c99b0d61d80b885b8c2
Source dataset
uspto-grants-2015_09
Patent number
US09120805B2

Reaction notes

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