Tetrahydrofuran → HCID 10298560, compound

HRID 651765Notes

Reaction equation

HRID 651765 reaction equation
CC([O-])(C)C.[K+].C1COCC1.[C:12]([C:14]1[CH:22]=[C:21]2[C:17]([C:18]([C:24](=O)[C:25]([O:27]C)=O)=[CH:19][N:20]2[CH3:23])=[CH:16][CH:15]=1)#[N:13].[CH3:30][N:31]1[C:39]2[C:34](=[CH:35][CH:36]=[C:37]([N:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)[CH:38]=2)[C:33]([CH2:46][C:47]([NH2:49])=[O:48])=[CH:32]1>>[CH3:23][N:20]1[C:21]2[C:17](=[CH:16][CH:15]=[C:14]([C:12]#[N:13])[CH:22]=2)[C:18]([C:24]2[C:25](=[O:27])[NH:49][C:47](=[O:48])[C:46]=2[C:33]2[C:34]3[C:39](=[CH:38][C:37]([N:40]4[CH2:41][CH2:42][O:43][CH2:44][CH2:45]4)=[CH:36][CH:35]=3)[N:31]([CH3:30])[CH:32]=2)=[CH:19]1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 21709057HCID 21709057, compoundHCID 23665647Potassium tert-butoxideHCID 86757286HCID 86757286, compound

Product 1

HCID 10298560HCID 10298560, compoundYield 69.2%

Procedure

A solution of t-BuOK in THF (1 M, 18.9 mL, 18.9 mmol) was added dropwise to a mixture of methyl (6-cyano-1-methyl-1H-indol-3-yl)glyoxylate (1.85 g, 7.64 mmol) and (1-methyl-6-morpholin-4-yl-1H-indol-3-yl)-acetamide (1.74 g, 6.36 mmol) at 0° C. The cooling bath was removed after 15 min and the mixture was stirred at room temperature for 3 h. Concentrated hydrochloric acid (37%, 10 mL) was added and the reaction mixture was stirred for a further 30 min. The mixture was made basic with aqueous NaHCO3 and extracted with CHCl3 (3×500 mL). The combined organic extracts were washed with aqueous Na2CO3 and dried (K2CO3). The extracts were filtered through a pad of silica gel, then evaporation of the solvents and crystallization of the crude product from acetone/EtOAc gave 1-methyl-3-[4-(1-methyl-6-morpholin-4-yl-1H-indol-3-yl)-2,5 -dioxo-2,5-dihydro-1H-pyrrole-3-yl-]-1H-indole-6-carbonitrile (2.05 g, 69%). Ref: Faul, M. M.; Winneroski, L. L.; Krumrich, C. A. J. Org. (Chem. 1998, 63, 6053.

Workup

  1. customThe cooling bath was removed after 15 min
  2. additionConcentrated hydrochloric acid (37%, 10 mL) was added
  3. stirringthe reaction mixture was stirred for a further 30 min
  4. extractionextracted with CHCl3 (3×500 mL)
  5. washThe combined organic extracts were washed with aqueous Na2CO3
  6. dry with materialdried (K2CO3)
  7. filtrationThe extracts were filtered through a pad of silica gel
  8. customevaporation of the solvents and crystallization of the crude product from acetone/EtOAc

Sources & evidence

ORD record
ord-e1b8fbd618454087920457a29b3a1a7e
Source dataset
uspto-grants-2001_08
Patent number
US06281356B1

Reaction notes

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