Sodium Iodide → HCID 18665173, compound

HRID 1872027Notes

Reaction equation

HRID 1872027 reaction equation
[I-].[Na+].[CH2:3]1[CH:7]2[CH2:8][NH:9][CH2:10][CH:6]2[CH2:5][N:4]1[CH2:11][CH2:12][CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([N:23]3[CH:27]=[N:26][N:25]=[CH:24]3)[CH:21]=2)[NH:16][CH:15]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[CH2:35][CH2:36][C:37]1[CH:42]=[CH:41][C:40]([NH:43][C:44](=[O:46])[CH3:45])=[CH:39][CH:38]=1>COCCOC>[N:26]1[N:25]=[CH:24][N:23]([C:20]2[CH:21]=[C:22]3[C:17](=[CH:18][CH:19]=2)[NH:16][CH:15]=[C:14]3[CH2:13][CH2:12][CH2:11][N:4]2[CH2:5][C@@H:6]3[CH2:10][N:9]([CH2:35][CH2:36][C:37]4[CH:42]=[CH:41][C:40]([NH:43][C:44](=[O:46])[CH3:45])=[CH:39][CH:38]=4)[CH2:8][C@@H:7]3[CH2:3]2)[CH:27]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 18690058HCID 18690058, compoundHCID 18690059HCID 18690059, compound

Product 1

HCID 18665173HCID 18665173, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

Sodium iodide (98 mg, 0.65 mmol) was added to a mixture of 3-(3-(hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)propyl)-5-(1,2,4-triazol-4-yl)-1H-indole (200 mg, 0.59 mmol), sodium carbonate (95 mg, 0.90 mmol) and N-(4-(2-bromoethyl)phenyl)acetamide (158 mg, 0.65 mmol) in dry 1,2-dimethoxyethane (5 ml) at room temperature under nitrogen. The mixture was then stirred and heated to reflux, protected from light, for 16 h. Upon cooling, the volatiles were removed in vacuo and the residue was partitioned between dichloromethane and water. The aqueous was further extracted with dichloromethane (x2). The combined extracts were dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with CH2Cl2 /MeOH/NH3 (60:8:1→50:8:1) to give the title indole (88 mg, 30%) as a foam. The bis hydrogen oxalate. 0.75 hydrate was prepared (Et2O/MeOH): mp 151-155° C. (Found: C, 57.43; H, 6.26; N, 14.35. C29H35N7O.2(C2H2O4).0.75(H2O) requires C, 57.34; H, 5.91; N, 14.18%). δ (360 MHz, d6 -DMSO) 1.94-2.02 (5H, m, includes NC(O)CH3), 2.7-3.3 (18H, m), 7.16 (2H, d, J=8.5 Hz, Ar--H), 7.30-7.36 (2H, m, Ar--H), 7.48-7.52 (3H, m, Ar--H), 7.81 (1H, s, Ar--H), 9.03 (2H, s, Triazole-H), 9.89 (1H, s, N--H), 11.17 (1H, s, N--H).

Workup

  1. temperatureheated
  2. temperatureto reflux
  3. customfor 16 h
  4. temperatureUpon cooling
  5. customthe volatiles were removed in vacuo
  6. customthe residue was partitioned between dichloromethane and water
  7. extractionThe aqueous was further extracted with dichloromethane (x2)
  8. dry with materialThe combined extracts were dried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by chromatography on silica gel
  12. washeluting with CH2Cl2 /MeOH/NH3 (60:8:1→50:8:1)

Sources & evidence

ORD record
ord-6aedd1d5453e45f4a8be61af9269314c
Source dataset
uspto-grants-2000_08
Patent number
US06107321

Reaction notes

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