Benzyl Bromide → 3,3-Dibenzyl-5-(3,4,5-trimethoxy-phenyl)-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one

HRID 333172Notes

Reaction equation

HRID 333172 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[CH:14]=[C:15]3[CH2:21][C:20](=[O:22])[NH:19][C:16]3=[N:17][CH:18]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].CN(CCN(C)C)C.[Li][CH2:32][CH2:33][CH2:34][CH3:35].[CH2:36](Br)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.[CH2:44]1[CH2:48]OC[CH2:45]1>>[CH2:35]([C:21]1([CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:15]2[C:16](=[N:17][CH:18]=[C:13]([C:5]3[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)[CH:14]=2)[NH:19][C:20]1=[O:22])[C:34]1[CH:48]=[CH:44][CH:45]=[CH:32][CH:33]=1

Participants

6

Reactant 5

HCID 7498Benzyl BromideHCID 8028Tetrahydrofuran2×HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 667786575-(3,4,5-Trimethoxy-phenyl)-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-oneHCID 178418339Butyllithium

Product 1

HCID 462360463,3-Dibenzyl-5-(3,4,5-trimethoxy-phenyl)-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-oneYield 38%

Procedure

5-(3,4,5-Trimethoxy-phenyl)-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one (95 mg, 0.316 mmol) and TMEDA (96 μl, 0.623 mmol) were dissolved in anhydrous THF (4 ml) and cooled to −78° C. n-BuLi (1.6 M in hexanes, 415 μl, 0.664 mmol) was added dropwise. After completed addition stirring was continued for 1 hr at −78° C. Benzyl bromide (41.3 μl, 0.348 mmol) was added dropwise as a 10% solution in anh. THF. After completed addition the reaction was allowed to warm up to room temperature while stirring overnight. The reaction was quenched by the addition of MeOH, evaporated and partitioned between water and DCM. Silica gel chromatography eluting with 0-50% EtOAc:Hexanes yielded the title compound (47 mg, 38%). 1H NMR (CDCl3, 300 MHz): δ 8.83 (s, 1H), 8.18 (d, J=1.2 Hz, 1H), 7.19 (d, J=1.2 Hz, 1H), 7.14 (m, 6H), 6.99 (m, 4H), 6.61 (s, 2H), 3.96 (s, 6H), 3.90 (s, 3H), 3.30 (d, J=8.0 Hz, 2H), 3.26 (d, J=8.0 Hz, 2H).

Workup

  1. additionwas added dropwise
  2. additionaddition
  3. additionaddition the reaction
  4. stirringwhile stirring overnight
  5. customThe reaction was quenched by the addition of MeOH
  6. customevaporated
  7. custompartitioned between water and DCM
  8. washSilica gel chromatography eluting with 0-50% EtOAc

Sources & evidence

ORD record
ord-87b55b7faaf147d0b15ad63d5da067de
Source dataset
uspto-grants-2014_11
Patent number
US08877772B2

Reaction notes

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