N,N-dimethyl-4-(5-nitro-1H-indol-3-yl)cyclohex-3-enamine → N-(3-(4-(Dimethylamino)cyclohexyl)-1H-indol-5-yl)thiophene-2-carboximidamide

HRID 2043522Notes

Reaction equation

HRID 2043522 reaction equation
[CH3:1][N:2]([CH3:21])[CH:3]1[CH2:8][CH2:7][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)=[CH:5][CH2:4]1.I.CS[C:25]([C:27]1[S:28][CH:29]=[CH:30][CH:31]=1)=[NH:26]>C(O)C.[Pd]>[CH3:1][N:2]([CH3:21])[CH: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:25]([C:27]4[S:28][CH:29]=[CH:30][CH:31]=4)=[NH:26])[CH:16]=3)[NH:11][CH:10]=2)[CH2:5][CH2:4]1

Participants

5

Reactant 2

HCID 44430852N,N-dimethyl-4-(5-nitro-1H-indol-3-yl)cyclohex-3-enamineHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

Product 1

HCID 178482649N-(3-(4-(Dimethylamino)cyclohexyl)-1H-indol-5-yl)thiophene-2-carboximidamideYield 72.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent2×

Procedure

A solution of compound 112 (0.43 g, 1.506 mmol) in dry ethanol (5 mL) was treated with 10% Pd—C (0.04 g) and purged with hydrogen gas at room temperature. The reaction was stirred at the same temperature under a hydrogen atmosphere (balloon pressure) overnight (14 h). The reaction was filtered through a celite bed and washed with dry ethanol (2×5 mL). The combined ethanol layer was treated with thiophene-2-carboximidothioic acid methyl ester hydroiodide (0.85 g, 3.013 mmol) at room temperature and stirred for 24 h. The solvent was evaporated and crude material was diluted with sat. NaHCO3 solution (20 mL) and product was extracted into CH2Cl2 (2×25 mL). The combined CH2Cl2 layer was washed with brine (20 mL) and dried (Na2SO4). The solvent was evaporated and crude was purified by column chromatography on silica gel (2 M NH3 in methanol: CH2Cl2, 1:9) to obtain compound 116 (0.4 g, 72%, over two steps) as a yellow solid. mp 104-106° C.; 1H NMR (DMSO-d6) δ: 1.39-1.60 (m, 3H), 1.66-1.72 (m, 1H), 1.82-1.94 (m, 3H), 2.05-2.08 (m, 1H), 2.23 (s, 3H), 2.34 (s, 3H), 2.64-2.71 (m, 1H), 2.91-2.96 (m, 1H), 6.48 (brs, 1H), 6.64 (dd, 1H, J=1.5, 8.4 Hz), 6.99-7.05 (m, 2H), 7.10 (t, 1H, J=4.2 Hz), 7.27 (d, 1H, J=8.4 Hz), 7.60 (d, 1H, J=5.4 Hz), 7.71 (d, 1H, J=3.3 Hz), 10.57 (s, 1H); ESI-MS m/z (%): 367 (MH+, 31), 322 (18), 184 (100); ESI-HRMS calculated for C21H27N4S (MH+), Calculated: 367.1965; Observed: 367.1950.

Workup

  1. custompurged with hydrogen gas at room temperature
  2. filtrationThe reaction was filtered through a celite bed
  3. washwashed with dry ethanol (2×5 mL)
  4. stirringstirred for 24 h
  5. customThe solvent was evaporated
  6. additioncrude material was diluted with sat. NaHCO3 solution (20 mL) and product
  7. extractionwas extracted into CH2Cl2 (2×25 mL)
  8. washThe combined CH2Cl2 layer was washed with brine (20 mL)
  9. dry with materialdried (Na2SO4)
  10. customThe solvent was evaporated
  11. customcrude was purified by column chromatography on silica gel (2 M NH3 in methanol: CH2Cl2, 1:9)

Sources & evidence

ORD record
ord-6e835a099ea9403ebc69c4c1eb050cdf
Source dataset
uspto-grants-2013_11
Patent number
US08586620B2

Reaction notes

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