Iodoethane → (S)-tert-butyl 1-(6-cyano-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-4-yl)pyrrolidin-3-yl(ethyl)carbamate

HRID 60274Notes

Reaction equation

HRID 60274 reaction equation
[C:1]([C:3]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:7]3[N:20]=[CH:21][CH:22]=[C:23]([N:24]4[CH2:28][CH2:27][C@H:26]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:25]4)[C:6]=3[C:5]=2[CH:4]=1)#[N:2].[H-].[Na+].I[CH2:40][CH3:41]>O1CCCC1>[C:1]([C:3]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:7]3[N:20]=[CH:21][CH:22]=[C:23]([N:24]4[CH2:28][CH2:27][C@H:26]([N:29]([CH2:40][CH3:41])[C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:35])[CH3:34])[CH2:25]4)[C:6]=3[C:5]=2[CH:4]=1)#[N:2]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 58365035(S)-tert-butyl 1-(6-cyano-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-4-yl)pyrrolidin-3-ylcarbamate

Product 1

HCID 58365118(S)-tert-butyl 1-(6-cyano-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-4-yl)pyrrolidin-3-yl(ethyl)carbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-tert-butyl 1-(6-cyano-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-4-yl)pyrrolidin-3-ylcarbamate (700 mg, 1.0 mmol) in tetrahydrofuran (11 mL) was added sodium hydride as a 60% dispersion in mineral oil (140 mg, 3.4 mmol) followed by iodoethane (0.77 mL, 9.4 mmol) and reaction mixture was stirred overnight at ambient temperature. The reaction was quenched with water (0.1 mL), diluted with ethyl acetate (100 mL) and washed with water (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, concentrated in vacuo, and purified by flash chromatography (silica, 4 g, ISCO, 0-60% ethyl acetate in heptane) to afford the title compound as a white solid, which was used in the next step without any further purification (560 mg. 80%).

Workup

  1. customThe reaction was quenched with water (0.1 mL)
  2. additiondiluted with ethyl acetate (100 mL)
  3. washwashed with water (50 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. custompurified by flash chromatography (silica, 4 g, ISCO, 0-60% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-199814be794d400d9a593486e56c1d5f
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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