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

HRID 60277Notes

Reaction equation

HRID 60277 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]([N:29]([CH2:37][CH3:38])[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].C([O-])(=O)C.[Na+].[Br:44]Br>C(O)(=O)C.C(OCC)(=O)C>[Br:44][C:22]1[CH:21]=[N:20][C:7]2[N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:18])([CH3:19])[CH3:17])[C:9]3[CH:10]=[N:11][C:3]([C:1]#[N:2])=[CH:4][C:5]=3[C:6]=2[C:23]=1[N:24]1[CH2:28][CH2:27][C@H:26]([N:29]([CH2:37][CH3:38])[C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:34])[CH3:35])[CH2:25]1

Participants

6

Reactant 3

HCID 24408BromineHCID 517045Sodium AcetateHCID 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

Product 1

HCID 58365177(S)-tert-butyl 1-(3-bromo-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 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture 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-yl(ethyl)carbamate (125 mg, 0.23 mmol), sodium acetate (38 mg, 0.46 mmol), and bromine (36 μL, 0.7 mmol) in acetic acid (1 mL) was stirred at ambient temperature for 1 minute. The reaction mixture was diluted with ethyl acetate (50 mL), and washed with water (20 mL). The organic layer was separated, dried over sodium sulfate, filtered, concentrated in vacuo, and purified by flash chromatography (silica, 4 g, ISCO, 0-50% ethyl acetate in heptane) to afford the title compound as a pale yellow oil, which was used in the next step without any further purification (65 mg).

Workup

  1. washwashed with water (20 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. custompurified by flash chromatography (silica, 4 g, ISCO, 0-50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-ebae6ef5eb0845cbaeacb405def14a81
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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