Methanol → HCID 10161023, compound

HRID 651773Notes

Reaction equation

HRID 651773 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[C:4]([C:13]2[C:14](=O)[O:15][C:16](=[O:33])[C:17]=2[C:18]2[C:26]3[C:21](=[CH:22][C:23]([N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)=[CH:24][CH:25]=3)[N:20]([CH3:32])[CH:19]=2)=[CH:3]1.CO.C[Si](C)(C)[NH:39][Si](C)(C)C>CN(C=O)C.C(OCC)(=O)C>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[C:4]([C:13]2[C:14](=[O:15])[NH:39][C:16](=[O:33])[C:17]=2[C:18]2[C:26]3[C:21](=[CH:22][C:23]([N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)=[CH:24][CH:25]=3)[N:20]([CH3:32])[CH:19]=2)=[CH:3]1

Participants

6

Reactant 3

HCID 887Methanol2×HCID 13838Hexamethyldisilazane2×HCID 21709056HCID 21709056, compound

Product 1

HCID 10161023HCID 10161023, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-Methyl-3-[4-(1-methyl-6-pyrrolidin-1-yl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-furan-3-yl]-1H-indole-6-carbonitrile (0.16 g, 0.36 mmol) was dissolved in dry DMF (5 mL, dried over 3A° molecular sieves) in a 50 mL round bottom flask. To this was added methanol (0.1 mL) and 1,1,1,3,3,3 hexamethyldisilazane (0.9 mL). The purple solution was stirred at room temperature overnight. Methanol (0.03 mL) and 1,1,1,3,3,3 hexamethyldisilazane (0.27 mL) were added and stirred for 3 h. The mixture was diluted with ethyl acetate (50 mL) and washed with brine. The aqueous layer was back extracted with ethyl acetate (2×50 mL). The combined organic extracts were diluted with an equal volume of hexanes, dried (MgSO4), and passed over a pad of silica gel. The silica gel was washed a with 1:1 ethyl acetate/hexanes (150 mL), and the filtrate was concentrated. Chromatography of the residue over silica gel using 25%-40% EtOAc/hexanes gave 1-methyl-3-[4-(1-methyl-6-pyrrolidin-1-yl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-yl]-1H-indole-6-carbonitrile (71 mg, 44%) as a purple solid.

Workup

  1. stirringstirred for 3 h
  2. washwashed with brine
  3. extractionThe aqueous layer was back extracted with ethyl acetate (2×50 mL)
  4. additionThe combined organic extracts were diluted with an equal volume of hexanes
  5. dry with materialdried (MgSO4)
  6. washThe silica gel was washed a with 1:1 ethyl acetate/hexanes (150 mL)
  7. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-174673c116e94b3a9708355e70f39a08
Source dataset
uspto-grants-2001_08
Patent number
US06281356B1

Reaction notes

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