HCID 57474453, compound → HCID 178462534, compound

HRID 2043499Notes

Reaction equation

HRID 2043499 reaction equation
[CH2:1]([N:3]1[CH2:8][CH:7]=[C:6]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([N+:18]([O-])=O)[CH:16]=3)[NH:11][CH:10]=2)[CH2:5][CH2:4]1)[CH3:2].I.CS[C:24]([C:26]1[S:27][CH:28]=[CH:29][CH:30]=1)=[NH:25]>C(O)C.[Pd]>[CH2:1]([N:3]1[CH2:8][CH2:7][CH:6]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([NH:18][C:24]([C:26]4[S:27][CH:28]=[CH:29][CH:30]=4)=[NH:25])[CH:16]=3)[NH:11][CH:10]=2)[CH2:5][CH2:4]1)[CH3:2]

Participants

5

Reactant 2

HCID 57474453HCID 57474453, compoundHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

Product 1

HCID 178462534HCID 178462534, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent2×

Procedure

A solution of 3-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)-5-nitro-1H-indole (60) (0.1 g, 0.368 mmol) in dry ethanol (5 mL) was treated with 10% Pd—C (0.02 g), purged with hydrogen gas and stirred for 4 h under hydrogen atm. (balloon pressure). The solid was filtered off using celite bed and washed with dry ethanol (2×5 mL). The combined ethanol layer was treated with thiophene-2-carboximidothioic acid methyl ester hydroiodide (0.21 g, 0.737 mmol) and stirred for 24 h at room temperature. The solvent was evaporated and product was precipitated with ether (100 mL). The solid was filtered and dissolved into sat. NaHCO3 sol.: CH2Cl2 (50 mL, 1:1). The org. layer was separated and aqueous layer was extracted with CH2Cl2 (2×20 mL). The combined CH2Cl2 layer was washed with brine (15 mL) and dried (Na2SO4). The solvent was evaporated and crude was purified by column chromatography (2M NH3 in methanol: CH2Cl2, 5:95) to obtain N-(3-(1-ethylpiperidin-4-yl)-1H-indol-5-yl)thiophene-2-carboximidamide (61) (0.085 g, 66%) as a solid. mp 150-152° C.; 1H NMR (DMSO-d6) δ1.01 (t, 3H, J=6.9 Hz), 1.59-1.75 (m, 2H), 1.90-2.05 (m, 4H), 2.35 (q, 2H), 2.65-2.73 (m, 1H), 2.94-2.97 (m, 2H), 6.23 (brs, 1H), 6.62 (dd, 1H, J=1.2, 8.4 Hz), 6.97 (s, 1H), 7.02 (d, 1H, J=2.1 Hz), 7.09 (t, 1H, J=4.2 Hz), 7.26 (d, 1H, J=8.4 Hz), 7.58 (d, 1H, J=5.4 Hz), 7.70 (d, 1H, J=3.6 Hz), 10.59 (s, 1H); ESI-MS m/z (%): 353 (M+, 100).

Workup

  1. custompurged with hydrogen gas
  2. filtrationThe solid was filtered off
  3. washwashed with dry ethanol (2×5 mL)
  4. stirringstirred for 24 h at room temperature
  5. customThe solvent was evaporated
  6. customproduct was precipitated with ether (100 mL)
  7. filtrationThe solid was filtered
  8. dissolutiondissolved into sat. NaHCO3 sol.
  9. customlayer was separated
  10. extractionaqueous layer was extracted with CH2Cl2 (2×20 mL)
  11. washThe combined CH2Cl2 layer was washed with brine (15 mL)
  12. dry with materialdried (Na2SO4)
  13. customThe solvent was evaporated
  14. customcrude was purified by column chromatography (2M NH3 in methanol: CH2Cl2, 5:95)

Sources & evidence

ORD record
ord-9b226ca8cf66486ab16fd6fc3ef934bf
Source dataset
uspto-grants-2013_11
Patent number
US08586620B2

Reaction notes

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