Citric Acid → (R)-6-Amino-alpha-[[(1(R)-methyl-2-(1H-indol-3-yl)ethyl)amino]methyl]-3-pyridinemethanol Citrate

HRID 1086480Notes

Reaction equation

HRID 1086480 reaction equation
[CH3:1][C@@H:2]([NH:13][CH2:14][C@@H:15]([C:17]1[CH:18]=[CH:19][C:20]2[N:21](N=N[N:25]=2)[CH:22]=1)[OH:16])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.O.O.Cl[Sn]Cl.[C:31]([OH:43])(=[O:42])[CH2:32][C:33]([CH2:38][C:39]([OH:41])=[O:40])([C:35]([OH:37])=[O:36])[OH:34]>CO.C(O)C>[C:31]([OH:43])(=[O:42])[CH2:32][C:33]([CH2:38][C:39]([OH:41])=[O:40])([C:35]([OH:37])=[O:36])[OH:34].[NH2:25][C:20]1[N:21]=[CH:22][C:17]([C@H:15]([CH2:14][NH:13][C@H:2]([CH3:1])[CH2:3][C:4]2[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[NH:6][CH:5]=2)[OH:16])=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 311Citric AcidHCID 61436Stannous chloride dihydrateHCID 15137721(R)-alpha-[[(1(R)-methyl-2-(1H-indol-3-yl)ethyl)amino]-methyl]tetrazolo[1,5-a]pyridine-6-methanol

Product 1

HCID 18645968(R)-6-Amino-alpha-[[(1(R)-methyl-2-(1H-indol-3-yl)ethyl)amino]methyl]-3-pyridinemethanol Citrate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

A solution of 0.5 g of this tetrazole in 15 ml of methanol is treated with 0.6 g of SnCl2.2H2O for 5 hours at reflux under nitrogen. The reaction mixture is partially concentrated and then poured into a mixture of 25 ml of CH2Cl2 and 15 ml of 1N NaOH solution. The layers are separated and the aqueous layer further extracted with CH2Cl2. The combined organic phases are backwashed with saturated sodium chloride solution and dried with anhydrous magnesium sulfate. Concentration of this solution and chromatography on silica gel affords the product which is dissolved in ethanol and treated with one equivalent of an ethanolic solution of citric acid. The mixture is aged for approximately one hour and the citrate salt is collected by filtration.

Workup

  1. temperatureat reflux under nitrogen
  2. concentrationThe reaction mixture is partially concentrated
  3. additionpoured into a mixture of 25 ml of CH2Cl2 and 15 ml of 1N NaOH solution
  4. customThe layers are separated
  5. extractionthe aqueous layer further extracted with CH2Cl2
  6. dry with materialdried with anhydrous magnesium sulfate
  7. customConcentration of this solution and chromatography on silica gel affords the product which
  8. filtrationthe citrate salt is collected by filtration

Sources & evidence

ORD record
ord-1ea56a8403d54f3b981beaa84015603d
Source dataset
uspto-grants-1991_07
Patent number
US05030640

Reaction notes

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