Imidazole → HCID 86754197, compound

HRID 581710Notes

Reaction equation

HRID 581710 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]([N:33]1[CH:37]=[CH:36]N=C1)(N1C=CN=C1)=[O:27].N1C=CN=C1.NCC[CH2:46][OH:47].C(Cl)[Cl:49]>>[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:33][CH2:37][CH2:36][CH2:46][OH:47])=[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 5

HCID 795ImidazoleHCID 6344Dichloromethane2×HCID 90863-Amino-1-propanolHCID 682631,1'-CarbonyldiimidazoleHCID 15863846HCID 15863846, compound

Product 1

HCID 86754197HCID 86754197, compound

Procedure

To a solution of 0.7 g (0.002 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 25 ml of CH2Cl2 under N2 and stirring, is added 0.36 g (0.0022 mole) of 1,1'-carbonyldiimidazole. After the imidazole intermediate formation is complete (as indicated by TLC, 45 hr), 0.75 g (0.01 mole) of 1-amino-3-propanol is added and the solution is allowed to stir for 4 days. The solution is concentrated and the residue is taken up in fresh CH2Cl2 and is washed with water until the washing is neutral. After drying over MgSO4, CH2Cl2 is evaporated under reduced pressure to yield a white sticky solid weighing 680 mg. The solid is dissolved in 7 ml of CH2Cl2 and is purified through a silica gel column (approx. 3×20 cm) first with 5% MeOH/CH2Cl2 (with approx. 7 ml of conc. NH4OH) and then with 10% MeOH/CH2Cl2 (10 ml conc. NH4OH). The fractions are collected, combined and concentrated. The residue is treated with ethanolic HCl to yield the analytically pure (3β,5β,14β,17β)-14-Amino-3-[[[(3-hydroxypropyl)amino]carbonyl]oxy]androstane-17-carboxylic Acid, Methyl Ester Hydrochloride Final Product.

Workup

  1. additionis added
  2. concentrationThe solution is concentrated
  3. washis washed with water until the washing
  4. dry with materialAfter drying over MgSO4, CH2Cl2
  5. customis evaporated under reduced pressure
  6. customto yield a white sticky solid
  7. customis purified through a silica gel column (approx. 3×20 cm) first with 5% MeOH/CH2Cl2 (with approx. 7 ml of conc. NH4OH)
  8. customThe fractions are collected
  9. concentrationconcentrated
  10. additionThe residue is treated with ethanolic HCl

Sources & evidence

ORD record
ord-23a146515970410e8531a0f6dc34ed7c
Source dataset
uspto-grants-1999_07
Patent number
US05922703

Reaction notes

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