Water → 3-[1-(2-naphthalenyl)-1H-indol-3-yl]-4-[1-[3-(1-pyrrolidinyl)propyl]-1H-indazol-3-yl]-1H-pyrrole-2,5-dione

HRID 968659Notes

Reaction equation

HRID 968659 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.CS(O[CH2:11][CH2:12][CH2:13][N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]([C:23]2[C:24](=[O:48])[NH:25][C:26](=[O:47])[C:27]=2[C:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]([C:37]3[CH:46]=[CH:45][C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[CH:38]=3)[CH:29]=2)=[N:15]1)(=O)=O.O>CC(N(C)C)=O>[CH:38]1[C:39]2[C:44](=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:45]=[CH:46][C:37]=1[N:30]1[C:31]2[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:28]([C:27]2[C:26](=[O:47])[NH:25][C:24](=[O:48])[C:23]=2[C:16]2[C:17]3[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=3)[N:14]([CH2:13][CH2:12][CH2:11][N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[N:15]=2)=[CH:29]1

Participants

5

Reactant 3

HCID 962WaterHCID 31268PyrrolidineHCID 225919653-[1-[3-[(methylsulfonyl)oxy]propyl]-1H-indazol-3-yl]-4-[1-(2-naphthalenyl)-1H-indol-3-yl]-1H-pyrrole-2,5-dione

Product 1

HCID 101880213-[1-(2-naphthalenyl)-1H-indol-3-yl]-4-[1-[3-(1-pyrrolidinyl)propyl]-1H-indazol-3-yl]-1H-pyrrole-2,5-dioneYield 18%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
65 °C

Procedure

Pyrrolidine (1 mL) was added to the 3-[1-[3-[(methylsulfonyl)oxy]propyl]-1H-indazol-3-yl]-4-[1-(2-naphthalenyl)-1H-indol-3-yl]-1H-pyrrole-2,5-dione (0.5 g, 0.975 mmol) in DMA (10 mL). The mixture was heated to 65° C. for 3 h, then cooled to rt. Water (5 mL) was added, followed by extraction with EtOAc (3×50 mL). The organic layers were combined, washed with H2O and brine, then dried (Na2SO4) and evaporated in vacuo to a dark brown oil. The oil was purified by flash column chromatography (97:3:0.3; DCM:MeOH:NH4OH) to afford Compound 85 (0.1 g, 18%) as an orange flaky solid. Compound 85 was dissolved in excess dilute HCl, then frozen and lyophilized to give the hydrochloride salt. 1H NMR (CD3OD) δ 8.22 (s, 1H), 8.01 (d, J=8.8 Hz, 1H), 7.89 (m, 3H), 7.49 (m, 7H), 7.00 (m, 2H), 6.64 (t, J=7.5 Hz, 1H), 6.39 (d, J=8.1 Hz, 1H), 4.47 (t, J=6.2 Hz, 2H), 3.44 (m, 2H), 3.07 (t, J=7.4 Hz, 2H), 2.82 (m, 2H), 2.16 (m, 2H), 1.93 (m, 4H). ES-MS m/z 566 (MH+).

Workup

  1. temperaturecooled to rt
  2. extractionfollowed by extraction with EtOAc (3×50 mL)
  3. washwashed with H2O and brine
  4. dry with materialdried (Na2SO4)
  5. customevaporated in vacuo to a dark brown oil
  6. customThe oil was purified by flash column chromatography (97:3:0.3; DCM:MeOH:NH4OH)

Sources & evidence

ORD record
ord-b444c8f9b88b43c797787c74a354e8c2
Source dataset
uspto-grants-2007_12
Patent number
US07304060B2

Reaction notes

Loading…