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

HRID 60275Notes

Reaction equation

HRID 60275 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].[Cl:39]N1C(=O)CCC1=O>C(#N)C.C(O)(C)C>[Cl:39][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

5

Reactant 2

HCID 31398ChlorosuccinimideHCID 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 58365160(S)-tert-butyl 1-(3-chloro-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 3776IsopropanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
35 °C

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 (100 mg, 0.2 mmol) and N-chlorosuccinimide (75 mg, 0.56 mmol) in acetonitrile (0.75 mL) and isopropyl alcohol (0.2 mL) was stirred at 35° C. for 5 hours. The cooled reaction mixture was quenched with saturated aqueous sodium thiosulfate, 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 foam, which was used in the next step without any further purification (100 mg).

Workup

  1. customThe cooled reaction mixture
  2. customwas quenched with saturated aqueous sodium thiosulfate
  3. additiondiluted with ethyl acetate (50 mL)
  4. washwashed with water (20 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by flash chromatography (silica, 4 g, ISCO, 0-50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-bfa1ca1bbd76401a9da30c396bb0b163
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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