Dichloromethane → HCID 86754200, compound

HRID 581716Notes

Reaction equation

HRID 581716 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)=[S:27].[NH2:38][C@@H:39]([CH:42]([CH3:44])[CH3:43])[CH2:40][OH:41].C(Cl)[Cl:46]>>[ClH:46].[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]([CH2:40][OH:41])[CH:42]([CH3:44])[CH3:43])=[S: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

5

Reactant 4

HCID 6344DichloromethaneHCID 802641,1'-Thiocarbonyldiimidazole2×HCID 640993L-ValinolHCID 15863846HCID 15863846, compound

Product 1

HCID 86754200HCID 86754200, compound

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 50 ml of CH2Cl2 under N2 and stirring, 0.78 g (0.0044 mole) of 1,1'-thiocarbonyldiimidazole is added. After 2 days of stirring at ambient temperature, the solution is heated at reflux overnight and an additional 0.16 g (0.0009 mole) of 1,1'-thiocarbonyldiimidazole is added. The solution is allowed to stir further at ambient temperature for 3 days; then 2.06 g (0.02 mole) of (S)-2-amino-3-methyl-1-butanol is added to the reaction mixture. The solution is allowed to stir for another 3 days and the solvent is then removed under reduced pressure. The residue is taken up in fresh CH2Cl2, washed with H2O until the washing is neutral. After drying over MgSO4, CH2Cl2 is removed under reduced pressure to yield the crude free base. The solid is purified by flash chromatography and then converted to its hydrochloride salt by the treatment with ethanolic HCl to yield analytically pure (3β(S),5β,14β,17β)-14-Amino-14-Amino-3-[[[(l-hydroxymethyl-2-methylpropyl)amino]thioxomethyl]oxy]androstane-17-carboxylic Acid, Methyl Ester Hydrochloride Final Product.

Workup

  1. temperaturethe solution is heated
  2. temperatureat reflux overnight
  3. stirringto stir further at ambient temperature for 3 days
  4. stirringto stir for another 3 days
  5. customthe solvent is then removed under reduced pressure
  6. washwashed with H2O until the washing
  7. dry with materialAfter drying over MgSO4, CH2Cl2
  8. customis removed under reduced pressure
  9. customto yield the crude free base
  10. customThe solid is purified by flash chromatography

Sources & evidence

ORD record
ord-f4024dd0cb5f4fd8a73d41180a968b21
Source dataset
uspto-grants-1999_07
Patent number
US05922703

Reaction notes

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