Phosphorus oxychloride → HCID 46898366, compound

HRID 602810Notes

Reaction equation

HRID 602810 reaction equation
[C:1]1([S:7]([C:10]([CH:20]2[CH2:32][C:23]3[NH:24][C:25]4[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][C:30]=4[C:22]=3[CH2:21]2)([F:19])[C:11]2[O:15][N:14]=[C:13]([C:16]([NH2:18])=O)[N:12]=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Cl)(Cl)(Cl)=O>C(#N)C>[C:1]1([S:7]([C:10]([CH:20]2[CH2:32][C:23]3[NH:24][C:25]4[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][C:30]=4[C:22]=3[CH2:21]2)([F:19])[C:11]2[O:15][N:14]=[C:13]([C:16]#[N:18])[N:12]=2)(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychloride2×HCID 11340480HCID 11340480, compound

Product 1

HCID 46898366HCID 46898366, compoundYield 12.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 170 mg (0.35 mmol) of (RS,SR)-5-[benzenesulfonyl-(7-chloro-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl)-fluoro-methyl]-[1,2,4]oxadiazole-3-carboxylic acid amide in 2 mL acetonitrile at RT was added 0.5 mL phosphorous oxychloride. The dark brown solution was stirred for 1 hour and then the temperature was raised to 50° C. and stirred overnight. After cooling down to RT, 0.5 mL phosphorous oxychloride were added. The reaction mixture was stirred for 2 hours under reflux condition. The solvent was partially evaporated and the resulting oil was dissolved with EtOAc and washed with saturated NaHCO3 solution. The organic phase was dried over Na2SO4, filtered and evaporated. Column chromatography on silica gel (EtOAc/heptane 1:1) yielded 20 mg (12%) (RS, SR)-5-[benzenesulfonyl-(7-chloro-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl)-fluoro-methyl]-[1,2,4]oxadiazole-3-carbonitrile as a light red solid, MS: 457 (MH+).

Workup

  1. stirringstirred overnight
  2. temperatureAfter cooling down to RT
  3. stirringThe reaction mixture was stirred for 2 hours
  4. temperatureunder reflux condition
  5. customThe solvent was partially evaporated
  6. dissolutionthe resulting oil was dissolved with EtOAc
  7. washwashed with saturated NaHCO3 solution
  8. dry with materialThe organic phase was dried over Na2SO4
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-4432f10497b24bfb8a9f579e73517c20
Source dataset
uspto-grants-2011_03
Patent number
US07906546B2

Reaction notes

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