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 2264388Notes

Reaction equation

HRID 2264388 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+). Using the procedure of Example 27 and the appropriate reagents and starting materials known to those skilled in the art, other compounds of the present invention may be prepared including, but not limited to:

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-470ca1bf6e3f4610af315f669075d101
Source dataset
uspto-grants-2010_12
Patent number
US07855203B2

Reaction notes

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