Phosphoric Acid → HCID 57474458, compound

HRID 2223808Notes

Reaction equation

HRID 2223808 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7]2)([O-:3])=[O:2].[CH3:13][N:14]1[CH:18]2[CH2:19][C:20]([CH2:22][CH:15]1[CH2:16][CH2:17]2)=O.OP(O)(O)=O>C(O)(=O)C>[CH3:13][N:14]1[CH:15]2[CH2:16][CH2:17][CH:18]1[CH2:19][C:20]([C:7]1[C:6]3[C:10](=[CH:11][CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[NH:9][CH:8]=1)=[CH:22]2

Participants

5

Reactant 3

HCID 1004Phosphoric AcidHCID 225235-NitroindoleHCID 79038Npc164516

Product 1

HCID 57474458HCID 57474458, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

A solution of 5-nitroindole (38) (0.5 g, 3.083 mmol) in glacial acetic acid (10 mL) was treated with tropinone (0.85 g, 6.617 mmol), followed by 2 M H3PO4 in glacial acetic acid (5 mL) at 100° C. and the resulting solution was stirred at same temperature for 24 h. The reaction was brought to room temperature, poured in to ice-cold 10% NH4OH solution (50 mL) and product was extracted into CH2Cl2 (2 25 mL). The combined CH2Cl2 layer was washed with brine (15 mL) and dried (Na2SO4). The solvent was evaporated and crude material was purified by column chromatography on silica gel (2 M NH3 in methanol: CH2Cl2, 1:9) to obtain compound 89 (0.27 g, 31%) as a solid. mp 234-236° C.; 1H NMR (DMSO-d6) δ 1.51-1.60 (m, 1H), 1.79-1.86 (m, 1H), 1.95-2.14 (m, 4H), 2.32 (s, 3H), 2.76-2.83 (m, 1H), 3.43 (t, 1H, J=5.4 Hz), 6.31 (d, 1H, J=5.1 Hz), 7.54 (d, 1H, J=8.7 Hz), 7.61 (s, 1H), 8.01 (dd, 1H, J=2.1, 9.0 Hz), 8.68 (d, 1H, J=2.4 Hz), 11.86 (s, 1H); ESI-MS m/z (%): 284 (MH+, 100). N-(3-(8-Methyl-8-azabicyclo[3.2.1]oct-3-en-3-yl)-1H-indol-5-yl)thiophene-2-carboximidamide (90): A solution of compound 89 (0.25 g, 0.882 mmol) in dry ethanol (10 mL) was treated with Pd—C (0.025 g) and purged with hydrogen gas. The reaction was stirred under hydrogen atm. (balloon pressure) for overnight (14 h). The solid was filtered off using celite bed and washed with ethanol (2 5 mL). The combine d ethanol layer was treated with thiophene-2-carboximidothioic acid methyl ester hydroiodide (0.5 g, 1.764 mmol) at room temperature and stirred for 24 h. Ethanol was evaporated and crude material was basified with sat. NaHCO3 solution (20 mL) and product was extracted into CH2Cl2 (2 25 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 on silica gel (2 M NH3 in methanol: CH2Cl2, 1:9) to obtain compound 90 (0.14 g, 44%) as a solid. mp 93-95° C.; 1H NMR (DMSO-d6) δ 1.60-1.65 (m, 1H), 1.84-1.90 (m, 1H), 2.02-2.26 (m, 4H), 2.41 (s, 3H), 2.83-2.89 (m, 1H), 3.46-3.55 (m, 1H), 6.20 (brs, 2H), 6.67 (d, 1H, J=7.8 Hz), 7.10 (s, 1H), 7.23-7.31 (m, 3H), 7.60-7.72 (m, 2H), 10.99 (s, 1H); ESI-MS m/z (%): 363 (MH+, 65), 182 (100), 119 (48); ESI-HRMS calculated for C21H23N4S (MH+), Calculated: 363.1633; Observed: 363.1637.

Workup

  1. customwas brought to room temperature
  2. extractionwas extracted into CH2Cl2 (2 25 mL)
  3. washThe combined CH2Cl2 layer was washed with brine (15 mL)
  4. dry with materialdried (Na2SO4)
  5. customThe solvent was evaporated
  6. customcrude material was purified by column chromatography on silica gel (2 M NH3 in methanol: CH2Cl2, 1:9)

Sources & evidence

ORD record
ord-54f1a92aa9ca429e8b22bd26263c7e17
Source dataset
uspto-grants-2008_05
Patent number
US07375219B2

Reaction notes

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