3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1H-indol-5-amine → HCID 178511959, compound

HRID 552969Notes

Reaction equation

HRID 552969 reaction equation
CN[CH:3]1[CH2:8][CH2:7][C:6]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([NH:18][C:19]([C:21]4[S:22][CH:23]=[CH:24][CH:25]=4)=[NH:20])[CH:16]=3)[NH:11][CH:10]=2)=[CH:5][CH2:4]1.C1C2[N:29]([CH2:30]C=C(C3C4C(=CC=C(N)C=4)NC=3)C2)[CH2:28]C1.I.CSC(C1SC=CC=1)=N>C(O)C>[CH2:3]1[CH:4]2[N:29]([CH2:30][CH:7]=[C:6]([C:9]3[C:17]4[C:12](=[CH:13][CH:14]=[C:15]([NH:18][C:19]([C:21]5[S:22][CH:23]=[CH:24][CH:25]=5)=[NH:20])[CH:16]=4)[NH:11][CH:10]=3)[CH2:5]2)[CH2:28][CH2:8]1

Participants

5

Reactant 3

HCID 537825203-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1H-indol-5-amineHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodideHCID 178482098HCID 178482098, compound

Product 1

HCID 178511959HCID 178511959, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of compound 141 (0.12 g, 0.423 mmol) in dry methanol (5 mL) was treated with Ra—Ni (˜0.05 g), hydrazine hydrate (0.13 mL, 4.235 mmol) at room temperature. The resulting mixture was refluxed for 2 min, in pre-heated oil bath. The reaction was brought to room temperature, filtered through celite bed and washed with methanol (2 20 mL). The combined methanol layer was evaporated and crude was purified by column chromatography (2 M NH3 in MeOH: CH2Cl2, 95:5) to obtain 3-(1,2,3,5,8,8a-Hexahydroindolizin-7-yl)-1H-indol-5-amine, (0.087 g, 81%) as a solid. mp 208-210° C.; 1H NMR (DMSO-d6) δ 1.33-1.48 (m, 1H), 1.67-1.79 (m, 2H), 1.94-2.13 (m, 2H), 2.16-2.26 (m, 2H), 2.58-2.65 (m, 1H), 2.85 (d, 1H, J=15.6 Hz), 3.08-3.17 (m, 1H), 3.59 (dd, 1H, J=4.5, 15.7 Hz), 4.49 (s, 2H), 6.01 (d, 1H, J=4.5 Hz), 6.48 (dd, 1H, J=1.8, 9.1 Hz), 7.01 (d, 1H, J=1.5 Hz), 7.05 (d, 1H, J=8.4 Hz), 7.17 (d, 1H, J=2.7 Hz), 10.60 (s, 1H); ESI-MS (m/z, %) 254 (MH+, 62), 185 (100). A solution of the amine (0.053 g, 0.209 mmol) in dry ethanol (3 mL) was treated with thiophene-2-carboximidothioic acid methyl ester hydroiodide (0.12 g, 0.418 mmol) at room temperature and the solution was stirred for 24 h. Solvent was evaporated, crude was diluted with sat. NaHCO3 solution (20 mL) and product was extracted into CH2Cl2 (2 20 mL). The combined CH2Cl2 layer was washed with brine (15 mL) and dried (Na2SO4). Solvent was evaporated and crude was purified by column chromatography (2 M NH3 in MeOH: CH2Cl2, 5:95) to obtain compound 142 (0.06 g, 79%) as a solid. mp 122-124° C.; 1H NMR (DMSO-d6) δ 1.38-1.46 (m, 1H), 1.70-1.78 (m, 2H), 1.93-2.12 (m, 2H), 2.20-2.28 (m, 2H), 2.62-2.72 (m, 1H), 2.83 (d, 1H, J=15.9 Hz), 3.07-3.13 (m, 1H), 3.59 (dd, 1H, J=4.5, 16.0 Hz), 6.07 (d, 1H, J=3.9 Hz), 6.22 (brs, 2H), 6.66 (d, 1H, J=8.1 Hz), 7.09 (dd, 1H, J=3.9, 4.9 Hz), 7.22 (s, 1H), 7.30-7.32 (m, 2H), 7.58 (d, 1H, J=4.5 Hz), 7.71 (d, 1H, J=2.7 Hz), 10.92 (s, 1H); ESI-MS (m/z, %) 363 (MH+, 20), 294 (100), 182 (15), ESI-HRMS calculated for C21H23N4S (MH+), calculated: 363.1655; observed: 363.1637.

Workup

  1. customSolvent was evaporated
  2. additioncrude was diluted with sat. NaHCO3 solution (20 mL) and product
  3. extractionwas extracted into CH2Cl2 (2 20 mL)
  4. washThe combined CH2Cl2 layer was washed with brine (15 mL)
  5. dry with materialdried (Na2SO4)
  6. customSolvent was evaporated
  7. customcrude was purified by column chromatography (2 M NH3 in MeOH: CH2Cl2, 5:95)

Sources & evidence

ORD record
ord-9491802b804c43138291ee0600d3c09e
Source dataset
uspto-grants-2011_05
Patent number
US07951940B2

Reaction notes

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