Hydrochloric Acid → HCID 86754198, compound

HRID 581714Notes

Reaction equation

HRID 581714 reaction equation
[NH2:1][C@@:2]12[C@H:19]3[C@@H:10]([C@:11]4([CH3:21])[C@H:16]([CH2:17][CH2:18]3)[CH2:15][C@@H:14]([OH:20])[CH2:13][CH2:12]4)[CH2:9][CH2:8][C@:6]1([CH3:7])[C@@H:5]([C:22]([O:24][CH3:25])=[O:23])[CH2:4][CH2:3]2.[C:26](N1C=CN=C1)(N1C=CN=C1)=[O:27].[NH2:38][C@@H:39]([CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[CH2:40][OH:41].[ClH:49]>C(Cl)Cl>[ClH:49].[NH2:1][C@@:2]12[C@H:19]3[C@@H:10]([C@:11]4([CH3:21])[C@H:16]([CH2:17][CH2:18]3)[CH2:15][C@@H:14]([O:20][C:26]([NH:38][CH:39]([CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[CH2:40][OH:41])=[O:27])[CH2:13][CH2:12]4)[CH2:9][CH2:8][C@:6]1([CH3:7])[C@@H:5]([C:22]([O:24][CH3:25])=[O:23])[CH2:4][CH2:3]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 447213phenylalaninol, (S)-HCID 15863846HCID 15863846, compound

Product 1

HCID 86754198HCID 86754198, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1.4 g (0.004 mole) of (3β,5β,14β,17β)-14-Amino-3-hydroxyandrostane-17-carboxylic Acid, Methyl Ester, prepared according to the procedure described in U.S. Pat. No. 4,885,280, incorporated by reference herein, in 40 ml of CH2Cl2 under N2 and stirring, is added 0.72 g (0.0044 mole) of 1,1'-carbonyldiimidazole. The solution is allowed to stir for 2 days and then 1.8 g (0.012 mole) of (S)-2-amino-3-phenyl-1-propanol is added. No product appeared to form (TLC) after 3 days of stirring and an additional 0.6 g (0.004 mole) of the amine is added and the solution is heated at boiling for 2 days. After cooling to ambient temperature, the solution is allowed to stir further for an additional 10 days. The solution is concentrated at reduced pressure and the residue is taken up with fresh CH2Cl2. The solution is washed with water until the washing is neutral. After drying over MgSO4, CH2Cl2 is removed under reduced pressure and the residual solid is purified by flash chromatography (5% MeOH/CH2Cl2, NH4OH). The fractions are combined and concentrated to yield the free base which is treated with ethanolic HCl to yield (3β(S),5β,14β,17β)-14-Amino-3-[[[[2-hydroxy-1-(phenylmethyl)ethyl]amino]carbonyl]oxy]androstane-17-carboxylic Acid, Methyl Ester Hydrochloride Final Product.

Workup

  1. customto form (TLC) after 3 days
  2. stirringof stirring
  3. temperaturethe solution is heated
  4. waitat boiling for 2 days
  5. stirringto stir further for an additional 10 days
  6. concentrationThe solution is concentrated at reduced pressure
  7. washThe solution is washed with water until the washing
  8. dry with materialAfter drying over MgSO4, CH2Cl2
  9. customis removed under reduced pressure
  10. customthe residual solid is purified by flash chromatography (5% MeOH/CH2Cl2, NH4OH)
  11. concentrationconcentrated
  12. customto yield the free base which

Sources & evidence

ORD record
ord-3c94de4c860940cfa0890929571a9a12
Source dataset
uspto-grants-1999_07
Patent number
US05922703

Reaction notes

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