Acetic Acid → N-Methyl-4-(5-nitro-1H-indol-3-yl)cyclohex-3-enamine

HRID 2043507Notes

Reaction equation

HRID 2043507 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[C:13]1[CH2:18][CH2:17][C:16](=O)[CH2:15][CH:14]=1)([O-:3])=[O:2].CC(O)=O.Cl.[CH3:25][NH2:26].[OH-].[Na+]>ClCCCl>[CH3:25][NH:26][CH:16]1[CH2:17][CH2:18][C:13]([C:7]2[C:6]3[C:10](=[CH:11][CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[NH:9][CH:8]=2)=[CH:14][CH2:15]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 6364545Methylamine hydrochlorideHCID 573845384-(5-nitro-1H-indol-3-yl)cyclohex-3-en-1-one

Product 1

HCID 57384539N-Methyl-4-(5-nitro-1H-indol-3-yl)cyclohex-3-enamineYield 99.9%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of compound 79 (0.07 g, 0.273 mmol) in 1,2-dichloroethane (3 mL) was treated with AcOH (0.015 mL, 0.273 mmol), methylamine hydrochloride (0.018 g, 0.273 mmol), NaBH(OAC)3 (0.086 g, 0.409 mmol) at room temperature and stirred for over night (14 h). The reaction was basified with 2 N NaOH (25 mL) and product was extracted into ethyl acetate (2×20 mL). The combined ethyl acetate layer was washed with brine (15 mL) and dried (Na2SO4). Solvent was evaporated and crude was purified by column chromatography (2 M NH3 in methanol: CH2Cl2, 1:9) to obtain compound 80 (0.074 g, quantitative) as a solid. mp 208-210° C.; 1H NMR (DMSO-d6) δ 1.44-1.53 (m, 1H), 1.97-2.01 (m, 2H), 2.35 (s, 3H), 2.40-2.57 (m, 3H), 2.60-2.70 (m, 1H), 6.13 (brs, 1H), 7.54 (d, 1H, J=9.0 Hz), 7.63 (s, 1H), 8.00 (d, 1H, J=7.5 Hz), 8.67 (s, 1H), 11.85 (brs, 1H); ESI-MS m/z (%): 272 (M+, 100).

Workup

  1. extractionwas extracted into ethyl acetate (2×20 mL)
  2. washThe combined ethyl acetate layer was washed with brine (15 mL)
  3. dry with materialdried (Na2SO4)
  4. customSolvent was evaporated
  5. customcrude was purified by column chromatography (2 M NH3 in methanol: CH2Cl2, 1:9)

Sources & evidence

ORD record
ord-1830e654e7d14b8890a7cc12ca081de2
Source dataset
uspto-grants-2013_11
Patent number
US08586620B2

Reaction notes

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