Dichloromethane → HCID 131721301, compound

HRID 581717Notes

Reaction equation

HRID 581717 reaction equation
N[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)[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(N1C=CN=C1)(N1C=CN=C1)=O.OCCN1CCNCC1.C(Cl)[Cl:48]>>[ClH:48].[ClH:48].[CH3:7][C@:6]12[CH2:8][CH2:9][C@H:10]3[C@@H:19]([CH2:18][CH2:17][CH:16]4[C@:11]3([CH3:21])[CH2:12][CH2:13][CH2:14][CH2:15]4)[C@@H:2]1[CH2:3][CH2:4][CH:5]2[C:22]([O:24][CH3:25])=[O:23]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 76771-(2-Hydroxyethyl)piperazineHCID 682631,1'-CarbonyldiimidazoleHCID 15863846HCID 15863846, compound

Product 1

HCID 131721301HCID 131721301, compound

Procedure

A stirred solution 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, (1.03 g, 2.95 mmole) in 25 ml of CH2Cl2 under a N2 blanket is treated with 1,1'-carbonyldiimidazole (0.58 g, 3.55 mmole). The mixture is stirred at room temperature for 24 hours and then treated with 4-hydroxyethyl-piperazine (1.92 g, 14.75 mmole). The reaction is continued to be stirred at room temperature under nitrogen overnight. The reaction solution is concentrated under reduced pressure and the residue is taken up in fresh CH2Cl2. The CH2Cl2 solution is washed with 4×25 ml portions of water. The organic layer is dried over anhydrous Na2SO4 and filtered. The filtrate is concentrated under reduced pressure to leave an oily residue weighing 0.94 g. The crude free base is purified by chromatography on silica gel packed column with an eluent of 5% MeOH/95% CH2Cl2 containing 1% NH4OH. The pure free base is dissolved in absolute alcohol and then treated with saturated ethanolic/HCl to yield (3β,5β,14β,17β)-14-Amino-3-[[[4-2-hydroxyethyl)-1-piperazinyl)carbonyl]oxy]androstane-17-carboxylic Acid, Methyl Ester Dihydrochloride Final Product.

Workup

  1. stirringto be stirred at room temperature under nitrogen overnight
  2. concentrationThe reaction solution is concentrated under reduced pressure
  3. washThe CH2Cl2 solution is washed with 4×25 ml portions of water
  4. dry with materialThe organic layer is dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate is concentrated under reduced pressure
  7. customto leave an oily residue
  8. customThe crude free base is purified by chromatography on silica gel
  9. dissolutionThe pure free base is dissolved in absolute alcohol
  10. additiontreated with saturated ethanolic/HCl

Sources & evidence

ORD record
ord-2178889281cb409aa42aab9d82aba323
Source dataset
uspto-grants-1999_07
Patent number
US05922703

Reaction notes

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