Ammonia → HCID 56591176, compound

HRID 931936Notes

Reaction equation

HRID 931936 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH2:21][CH:22]3[CH2:24][CH2:23]3)[C:11](=[O:25])[C@H:10]([CH2:26][C:27](OC)=[O:28])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[NH3:31].CO.[C-]#N.[Na+]>>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[N:12]([CH2:21][CH:22]3[CH2:23][CH2:24]3)[C:11](=[O:25])[C@H:10]([CH2:26][C:27]([NH2:31])=[O:28])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 222AmmoniaHCID 887MethanolHCID 8929Sodium CyanideHCID 58573166HCID 58573166, compound

Product 1

HCID 56591176HCID 56591176, compound

Conditions

Temperature
50 °C

Procedure

A sealed tube was charged with methyl 2-((3S,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-2-oxopiperidin-3-yl)acetate (Example 59, Step A) (109 mg, 0.244 mmol), ammonia, 7N solution in methanol (2 ml, 14.00 mmol) and sodium cyanide (1.197 mg, 0.024 mmol). The tube was sealed and heated to 50° C. The pressure reached 35 kilopascals after 1 hour. The reaction was stirred at 50° C. for 18 h. The reaction was cooled to rt and anhydrous ammonia (gas) was bubbled through the solution for ten minutes at room temperature. The reaction mixture was capped and heated to 50° C. for 18 h. The reaction was cooled to rt and anhydrous ammonia (gas) was bubbled through the solution for twenty minutes at room temperature. The reaction mixture was capped and heated to 50° C. for 2 days. The crude reaction was concentrated under reduced pressure and purified by reversed phase preparatory HPLC (column: Gemini-NX C18 5 um column; Phenomonex, Torrance, Calif.; eluent: 0 to 100% MeCN +0.1% TFA in water +0.1% TFA, over 20 minutes) to afford the title compound.

Workup

  1. customThe tube was sealed
  2. customafter 1 hour
  3. temperatureThe reaction was cooled to rt
  4. customanhydrous ammonia (gas) was bubbled through the solution for ten minutes at room temperature
  5. customThe reaction mixture was capped
  6. temperatureheated to 50° C. for 18 h
  7. temperatureThe reaction was cooled to rt
  8. customanhydrous ammonia (gas) was bubbled through the solution for twenty minutes at room temperature
  9. customThe reaction mixture was capped
  10. temperatureheated to 50° C. for 2 days
  11. customThe crude reaction
  12. concentrationwas concentrated under reduced pressure
  13. custompurified by reversed phase preparatory HPLC (column: Gemini-NX C18 5 um column; Phenomonex, Torrance, Calif.; eluent: 0 to 100% MeCN +0.1% TFA in water +0.1% TFA, over 20 minutes)

Sources & evidence

ORD record
ord-0e00e7af705b41df9c696f0c01d78d06
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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