Ammonia → HCID 67251150, compound

HRID 2427286Notes

Reaction equation

HRID 2427286 reaction equation
[CH:1]([O:4][C:5](=[O:29])[NH:6][CH:7]1[CH2:28][C:10]2[N:11]([CH2:20][C:21]3[C:26](Cl)=[N:25][CH:24]=[CH:23][N:22]=3)[C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2].[NH3:30]>CN1CCCC1=O>[CH:1]([O:4][C:5](=[O:29])[NH:6][CH:7]1[CH2:28][C:10]2[N:11]([CH2:20][C:21]3[C:26]([NH2:30])=[N:25][CH:24]=[CH:23][N:22]=3)[C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 222Ammonia2×HCID 86640057HCID 86640057, compound

Product 1

HCID 67251150HCID 67251150, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
-78 °C

Procedure

In a screw-cap vial, dissolve (±)-[4-(3-chloro-pyrazin-2-ylmethyl)-7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester (30 mL, 0.073 mmol) in 1-methyl-2-pyrrolidinone (NMP) (0.5 mL) and cool to −78° C. Condense NH3 into the reaction mixture (1 mL), seal the reaction vessel, and warm to room temperature over 24 h. Heat the reaction up to 50° C. for 18 h, then at 80° C. for 72 h. Cool the reaction in a dry ice bath. Carefully open the reaction vessel and allow the liquid NH3 to evaporate. Dissolve the residue in EtOAc (50 mL) and wash the organics with water (3×20 mL). Dry the organics (MgSO4), filter, and concentrate to give 27 mg crude product as a colorless film. Purify on 4 g silica gel [50-100% EtOAc/(1:1 CH2Cl2/hexanes)] to give 8 mg (28%) of the title compound as a colorless film. LCMS 100% @ 4.23 min m/z 391 (M+H), 389 (M−H).

Workup

  1. customseal the reaction vessel
  2. temperaturewarm to room temperature over 24 h
  3. temperatureHeat
  4. customthe reaction up to 50° C. for 18 h
  5. temperatureCool
  6. customthe reaction in a dry ice bath
  7. customto evaporate
  8. dissolutionDissolve the residue in EtOAc (50 mL)
  9. washwash the organics with water (3×20 mL)
  10. dry with materialDry the organics (MgSO4)
  11. filtrationfilter
  12. concentrationconcentrate
  13. customto give 27 mg crude product as a colorless film
  14. customPurify on 4 g silica gel [50-100% EtOAc/(1:1 CH2Cl2/hexanes)]

Sources & evidence

ORD record
ord-a947326e49d24168b6d8b31f41603b7a
Source dataset
uspto-grants-2011_06
Patent number
US07968587B2

Reaction notes

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