Sodium hydride → HCID 67610465, compound

HRID 964559Notes

Reaction equation

HRID 964559 reaction equation
[CH3:1][C:2]1[C:3]([C:19]([OH:21])=O)=[N:4][C:5]2[C:6]=1[C:7](C)=[C:8]1[C:16]([CH:17]=2)=[C:15]2[C:10]([CH:11]=[CH:12][CH:13]=[CH:14]2)=[N:9]1.[C:22]([C:29]1NC=CN=1)([C:24]1[NH:25]C=C[N:28]=1)=O.[N-]1C=CN=[CH:35]1.[H-].[Na+]>O1CCCC1.CCOCC>[CH3:1][C:2]1[C:3]([C:19]2[O:21][N:28]=[C:24]([CH2:22][CH3:29])[N:25]=2)=[N:4][C:5]2[C:17]=1[C:16]([CH3:35])=[C:8]1[C:7]([CH:6]=2)=[C:15]2[C:10]([CH:11]=[CH:12][CH:13]=[CH:14]2)=[N:9]1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 3386966ImidazolateHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 19367633HCID 19367633, compound

Product 1

HCID 67610465HCID 67610465, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

3,4-Dimethylpyrrolo[3,2-b]carbazole-2-carboxylic acid (2.78 g, 10.0 mmol), (prepared as described in WO93/01512) and carbonyl diimidazole (1.85 g, 11.4 mmol) were dissolved in freshly distilled tetrahydrofuran (50 ml) in an oven-dried flask under a nitrogen atmosphere. The resulting orange solution was stirred at room temperature for three hours, by which time it was an orange suspension, and complete conversion of the acid to the imidazolide intermediate was verified by TLC. Meanwhile, in a second oven-dried flask, ethylamidoxime (2.2 g, 25 mmol) was dissolved in THF (50 ml). To this was added crushed 3 Å sieves (3.3 g) and the mixture was stirred at room temp for 45 min. Sodium hydride (60% dispersion in mineral oil, 0.804 g, 20 mmol) was added and the mixture stirred for a further 2.5 hours. The contents of the two flasks were combined and stirred at room temp for 18 hours, by which time TLC showed complete consumption of the imidazolide intermediate. The solvent was removed in vacuo to give a yellow solid. Chromatography on silica (eluting with ethyl acetate/petrol, gradient 8% -15% ethyl acetate) gave a yellow solid. The majority of this material was dissolved in ether, leaving an insoluble orange impurity. The solution was filtered, and the solvent removed in vacuo to give the title compound as a yellow powder (1.2 g, 36%) which decomposes above 45° C. δH [2H6 ]-DMSO 11.69 (1H, s, 1-NH), 10.69 (1H, s, 5-NH), 8.09 (1H, d, J 7.5, 9-H), 7.90 (1H, s, 10-H), 7.30-7.48 (2H, m, 6-H, 7-H), 7.09 (1H ddd, J 7.5, 5.5, 2, 8-H), 2.99 and 2.95 (2×3H, 2×s, 3-CH3 and 4-CH3), 2.85 (2H, q, 7.5, CH2 CH3), 1.36 (3H, t, 7.5, CH2CH3).

Workup

  1. additionTo this was added
  2. customcrushed 3 Å
  3. stirringthe mixture was stirred at room temp for 45 min
  4. stirringthe mixture stirred for a further 2.5 hours
  5. stirringstirred at room temp for 18 hours, by which time TLC
  6. customconsumption of the imidazolide intermediate
  7. customThe solvent was removed in vacuo
  8. customto give a yellow solid
  9. customChromatography on silica (eluting with ethyl acetate/petrol, gradient 8% -15% ethyl acetate) gave a yellow solid
  10. customleaving an insoluble orange impurity
  11. filtrationThe solution was filtered
  12. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-486e0e4debbc468dafad990377dd377b
Source dataset
uspto-grants-1998_06
Patent number
US05770598

Reaction notes

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