Hydrochloric Acid → HCID 18975402, compound

HRID 2393407Notes

Reaction equation

HRID 2393407 reaction equation
[CH3:1][C:2]1([CH:19]([CH2:23][CH3:24])C(O)=O)[C:14]2[N:13]3[CH:15]=[CH:16][N:17]=[C:12]3[C:11](=[O:18])[NH:10][C:9]=2[C:8]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]1=2.C(Cl)(=O)[C:26](Cl)=[O:27].[BH4-].[BH4-].[BH4-].[BH4-].[Na+].[Na+].[Na+].[Na+].Cl>O1CCOCC1.CN(C)C=O.CO>[OH:27][CH2:26][CH2:24][CH2:23][CH2:19][C:2]1([CH3:1])[C:14]2[N:13]3[CH:15]=[CH:16][N:17]=[C:12]3[C:11](=[O:18])[NH:10][C:9]=2[C:8]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]1=2

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 65578Oxalyl chloride2×HCID 18975479HCID 18975479, compoundHCID 131720822Sodium tetraborohydride

Product 1

HCID 18975402HCID 18975402, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent3×HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
10 °C

Procedure

A stirred suspension of 0.6 g of (10-methyl-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indeno[1,2-e]-pyrazin-10-yl)butyric acid in 20 ml of dioxane is cooled to a temperature in the region of 10° C., under an argon atmosphere, and 0.19 ml of oxalyl chloride is added. A solution of 0.5 ml of dimethylformamide in 5 ml of dioxane is then added dropwise. After the addition, the mixture is left stirring for 4 hours at a temperature in the region of 20° C. A further 0.38 ml of oxalyl chloride and 6 ml of dimethylformamide are added dropwise and stirring is continued for 1 hour. A solution of 0.38 g of sodium tetraborohydride in 10 ml of dimethylformamide is then added dropwise and the stirring is continued overnight. The reaction mixture is treated with 10 ml of methanol, acidified to pH 1 with 1N hydrochloric acid and concentrated on a rotary evaporator. The evaporation residue is purified by chromatography on a column of silica (100 g) eluting, under a pressure of 0.5 bar, first with a dichloromethane/methanol mixture (95/5 by volume) and then with a dichloromethane/methanol/28% aqueous ammonia mixture (90/10/0.5 by volume). 70 mg of 10-(4-hydroxybutyl)-10-methyl-5H,10H-imidazo[1,2-a]indeno-[1,2-e]pyrazin-4-one are obtained in the form of a white solid (1H NMR spectrum [300 MHz; (CD3)2SO-d6 ; δ in ppm]: 0.52 (mt, 2H: CH2); 1.29 (quintet, J=7.5 Hz, 2H: CH2); 1.57 (s, 3H: CH3); 2.17 and 2.36 (2 mts, 1H each: hetero-CH2); 3.14 (t, J=7.5 Hz, 1H: CH2O); 4.19 (broad s, 1H: OH); 7.38 (mt, 2H: H 7 and H 8); 7.67 and 8.24 (2 broad s, 1H each: H of the imidazole); 7.60 and 7.87 (2 broad d, J=7.5 Hz, 1H each: H 6 and H9)).

Workup

  1. additionAfter the addition
  2. waitthe mixture is left
  3. stirringstirring
  4. waitis continued for 1 hour
  5. waitthe stirring is continued overnight
  6. concentrationconcentrated on a rotary evaporator
  7. customThe evaporation residue is purified by chromatography on a column of silica (100 g)
  8. washeluting, under a pressure of 0.5 bar, first with a dichloromethane/methanol mixture (95/5 by volume)

Sources & evidence

ORD record
ord-6acb112682ba4b73964d70d423b12f5d
Source dataset
uspto-grants-1998_09
Patent number
US05807859

Reaction notes

Loading…