Phosphorus oxychloride → N-[1-(3,5-Dimethoxyphenyl)-1-methylethyl]-3-cyanoandrosta-3,5-diene-17beta-carboxamide

HRID 962716Notes

Reaction equation

HRID 962716 reaction equation
P(Cl)(Cl)([Cl:3])=O.[CH3:6][N+:7]([CH3:10])=[CH:8][Cl:9].[Cl-].[C:12]([C:14]1[CH2:31][CH2:30][C@@:29]2([CH3:32])[C:16](=[CH:17][CH2:18][C@@H:19]3[C@@H:28]2[CH2:27][CH2:26][C@@:24]2([CH3:25])[C@H:20]3[CH2:21][CH2:22][C@@H:23]2[C:33](O)=[O:34])[CH:15]=1)#[N:13].[CH3:36][O:37][C:38]1[CH:39]=[C:40]([C:46]([NH2:49])([CH3:48])[CH3:47])[CH:41]=[C:42]([O:44][CH3:45])[CH:43]=1>C(Cl)Cl.C(OCC)(=O)C.CC(C)=O.C(N(CC)CC)C.CN(C)C=O>[CH3:6][N+:7]([CH3:10])=[CH:8][Cl:9].[Cl-:3].[CH3:45][O:44][C:42]1[CH:41]=[C:40]([C:46]([NH:49][C:33]([C@H:23]2[CH2:22][CH2:21][C@H:20]3[C@H:19]4[C@H:28]([CH2:27][CH2:26][C@:24]23[CH3:25])[C@:29]2([CH3:32])[C:16]([CH:15]=[C:14]([C:12]#[N:13])[CH2:31][CH2:30]2)=[CH:17][CH2:18]4)=[O:34])([CH3:47])[CH3:48])[CH:39]=[C:38]([O:37][CH3:36])[CH:43]=1

Participants

11

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 153802543-Cyanoandrosta-3,5-diene-17beta-carboxylic acidHCID 157541382-(3,5-Dimethoxyphenyl)propan-2-amine

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 57001892N-[1-(3,5-Dimethoxyphenyl)-1-methylethyl]-3-cyanoandrosta-3,5-diene-17beta-carboxamideYield 50%

Reagents, catalysts & solvents 5

HCID 180AcetoneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent4×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

Vilsmeier reagent was prepared from 1.7 ml of dimethylformamide, 1.8 ml of phosphorus oxychloride, and 5 ml of methylene chloride. 0.23 ml of this Vilsmeier reagent was then added to a solution of 100 mg of 3-cyanoandrosta-3,5-diene-17β-carboxylic acid [prepared as described in Example 1(b)] in 2 ml of methylene chloride. The reaction mixture was then stirred at room temperature for 40 minutes, after which a solution of 1-(3,5-dimethoxyphenyl)-1-methylethylamine [prepared as described in Preparation 10(d)] and 70 μl of triethylamine in 2 ml of methylene chloride were added. The reaction mixture was then diluted with ethyl acetate, washed with dilute aqueous hydrochloric acid, with an aqueous solution of sodium chloride, with a 5% w/v aqueous solution of sodium hydrogencarbonate, and with a saturated aqueous solution of sodium chloride, in that order. It was then dried over anhydrous magnesium sulfate, and concentrated by evaporation under reduced pressure. The resulting residue was subjected to silica gel column chromatography and using a gradient elution method, with solutions of from 1 to 4% by volume of acetone in methylene chloride as the eluent, to give 76 mg (yield 50%) of the title compound.

Workup

  1. washwashed with dilute aqueous hydrochloric acid, with an aqueous solution of sodium chloride, with a 5% w/v aqueous solution of sodium hydrogencarbonate
  2. dry with materialIt was then dried over anhydrous magnesium sulfate
  3. concentrationconcentrated by evaporation under reduced pressure
  4. washa gradient elution method

Sources & evidence

ORD record
ord-fba8eb42b5b945979706b26d528846d1
Source dataset
uspto-grants-1998_06
Patent number
US05760025

Reaction notes

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