Ethyl Acetate → 5'-Chloro-3-methyl-2'-oxo-1',2,2',3,4,9-hexahydrospiro[beta-carboline-1,3'-indol]-6-carbonitrile

HRID 555344Notes

Reaction equation

HRID 555344 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20]1[C:9]3([C:17]4[C:12](=[CH:13][CH:14]=[C:15]([Cl:18])[CH:16]=4)[NH:11][C:10]3=[O:19])[NH:8][CH:7]([CH3:25])[CH2:6][C:5]2=1.[C:26]([Cu])#[N:27].CCOC(C)=O>CN1CCCC1=O.CCCCCC>[Cl:18][C:15]1[CH:16]=[C:17]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10](=[O:19])[C:9]12[C:20]2[NH:21][C:22]3[C:4](=[CH:3][C:2]([C:26]#[N:27])=[CH:24][CH:23]=3)[C:5]=2[CH2:6][CH:7]([CH3:25])[NH:8]1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 57948762HCID 57948762, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 669870975'-Chloro-3-methyl-2'-oxo-1',2,2',3,4,9-hexahydrospiro[beta-carboline-1,3'-indol]-6-carbonitrile

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Compound 63 (30 mg, 0.072 mmol), CuCN (9.67 mg, 0.108 mmol) in N-methylpyrrolidone (0.12 mL) was refluxed for 16 hr. The solvent was removed under reduced pressure overnight and the black residue was stirred for 30 minutes with 30% aq. ammonia (0.2 mL), followed by addition of chloroform. An insoluble material was filtered off and washed 5 times with boiling chloroform. The organic phases were combined, washed with water and dried with sodium sulfate. The product was isolated using flash column chromatography with 10%-35% EtOAc in hexane (3.0 mg, 11.5%). 1H NMR (300 MHz, DMSO-d6): δ 11.11 (s, 1H), 10.54 (s, 1H), 7.99 (s, 1H), 7.92-7.83 (m, 3H), 7.05 (d, J=2.1 Hz, 1H), 6.94 (d, J=8.4 Hz, 1H), 3.98-3.85 (m, 1H), 2.85 (dd, J=15.5, 3.6 Hz, 1H), 2.42 (dd, J=15.3, 10.5 Hz, 1H), 1.18 (d, J=6.9 Hz, 3H); MS (ESI) m/z 363.0 (M+H)+.

Workup

  1. customThe solvent was removed under reduced pressure overnight
  2. additionfollowed by addition of chloroform
  3. filtrationAn insoluble material was filtered off
  4. washwashed 5 times with boiling chloroform
  5. washwashed with water
  6. dry with materialdried with sodium sulfate
  7. customThe product was isolated

Sources & evidence

ORD record
ord-6ce21af25bcf4907a79a07169f8d65df
Source dataset
uspto-grants-2011_11
Patent number
US08053442B2

Reaction notes

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