HCID 57474477, compound → HCID 178480156, compound

HRID 552978Notes

Reaction equation

HRID 552978 reaction equation
[CH2:1]([C:8]1[N:9]([CH2:20][CH2:21][CH:22]2[CH2:26][CH2:25][CH2:24][N:23]2[CH3:27])[C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[C:12]([N+:17]([O-])=O)[CH:11]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I.CS[C:31]([C:33]1[S:34][CH:35]=[CH:36][CH:37]=1)=[NH:32]>C(O)C.[Pd]>[CH2:1]([C:8]1[N:9]([CH2:20][CH2:21][CH:22]2[CH2:26][CH2:25][CH2:24][N:23]2[CH3:27])[C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[C:12]([NH:17][C:31]([C:33]1[S:34][CH:35]=[CH:36][CH:37]=1)=[NH:32])[CH:11]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 57474477HCID 57474477, compound2×HCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide3×

Product 1

HCID 178480156HCID 178480156, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

2-benzyl-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-nitro-1H-indole (compound 162, 40 mg, 0.110 mmol) was dissolved in anhydrous ethanol (5 mL) in a dry argon purged flask. Palladium, 10 wt % on activated carbon (11.7 mg, 0.011 mmol) is quickly added and the atmosphere from the flask evacuated by vacuum pump and replaced with hydrogen from a balloon. The atmosphere is evacuated from the flask and replaced with hydrogen twice more and the mixture stirred under a hydrogen atmosphere at room temperature. After 3 hours, thin layer chromatography in a solvent system of (5% 2M NH3 in methanol/95% dichloromethane) shows complete conversion to compound 163, 2-benzyl-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-1H-indol-6-amine, which is utilized without isolation. The mixture is filtered through a pad of celite to remove insolubles, the pad washed with anhydrous ethanol (5 mL) and the ethanolic solution of the amine 163 is charged to a small, argon purged flask fitted with a magnetic stirbar. Thiophene-2-carboximidothioic acid methyl ester hydroiodide (40.8 mg, 0.143 mmol) is added to the flask and the reaction was stirred under Ar at ambient temperature for 48 hours. An additional amount of the thiophene-2-carboximidothioic acid methyl ester hydroiodide (0.3 eq) was added and stirring continued for an additional 18 hours. A further portion of thiophene-2-carboximidothioic acid methyl ester hydroiodide (0.3 eq) was added and stirring continued for an additional 18 hours, at which time the mixture was concentrated and the residue purified via chromatography on silica gel (2.5% 2M NH3 in methanol/97.5% dichloromethane to 5% 2M NH3 in methanol/95% dichloromethane) to afford yellow oil, compound 164 (38 mg, 78.0% yield); 1H-NMR (CDCl3) δ 7.72 (d, 1H, J=3.2), 7.59 (d, 1H, J=4.7), 7.38 (d, 1H, J=8.1), 7.35-7.20 (m, 5H), 7.09 (m, 1H), 6.77 (s, 1H), 6.56 (d, 1H, J=7.4), 6.36 (br s, 2H), 6.14 (s, 1H), 4.14 (s, 2H), 3.96 (t, 2H, J=7.9), 2.94-2.86 (m, 1H), 2.09 (s, 3H), 2.06-1.94 (m, 2H), 1.89-1.78 (m, 1H), 1.69-1.51 (m, 3H), 1.45-1.35 (m, 2H); MS (ESI+): 443 (M+1, 70%) 219 (100%).

Workup

  1. customthe atmosphere from the flask evacuated by vacuum pump
  2. customThe atmosphere is evacuated from the flask
  3. filtrationThe mixture is filtered through a pad of celite
  4. customto remove insolubles
  5. washthe pad washed with anhydrous ethanol (5 mL)
  6. additionthe ethanolic solution of the amine 163 is charged to a small, argon purged flask
  7. customfitted with a magnetic stirbar
  8. stirringthe reaction was stirred under Ar at ambient temperature for 48 hours
  9. stirringstirring
  10. waitcontinued for an additional 18 hours
  11. stirringstirring
  12. waitcontinued for an additional 18 hours, at which time
  13. concentrationthe mixture was concentrated
  14. customthe residue purified via chromatography on silica gel (2.5% 2M NH3 in methanol/97.5% dichloromethane to 5% 2M NH3 in methanol/95% dichloromethane)

Sources & evidence

ORD record
ord-8fc8e3f2b28e4ecca682c87da649f404
Source dataset
uspto-grants-2011_05
Patent number
US07951940B2

Reaction notes

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