Sodium hydride → (R)-tert-butyl 3-(6-bromo-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-4-yloxy)piperidine-1-carboxylate

HRID 60318Notes

Reaction equation

HRID 60318 reaction equation
[OH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[H-].[Na+].[Br:17][C:18]1[N:26]=[CH:25][C:24]2[N:23]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:22]3[N:35]=[CH:36][CH:37]=[C:38](Cl)[C:21]=3[C:20]=2[CH:19]=1.BrC1N=CC2N(COCC[Si](C)(C)C)C3N=C(Cl)C=CC=3C=2C=1>O1CCCC1.O.C(OCC)(=O)C>[Br:17][C:18]1[N:26]=[CH:25][C:24]2[N:23]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:33])([CH3:34])[CH3:32])[C:22]3[N:35]=[CH:36][CH:37]=[C:38]([O:1][C@@H:2]4[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]4)[C:21]=3[C:20]=2[CH:19]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 1514398(R)-1-Boc-3-hydroxypiperidineHCID 583650426-Bromo-4-chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrroleHCID 866560476-bromo-2-chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

Product 1

HCID 58365164(R)-tert-butyl 3-(6-bromo-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-4-yloxy)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of (R)-tert-butyl 3-hydroxypiperidine-1-carboxylate (64 mg, 0.32 mmol) in tetrahydrofuran (1.2 mL) was added sodium hydride as 60% dispersion in mineral oil (13 mg, 0.32 mmol). The reaction mixture was stirred at ambient temperature for 5 minutes before a mixture of 6-bromo-4-chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole with 6-bromo-2-chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (4:1, 60 mg, 0.1 mmol) was added in one portion, and the reaction mixture was stirred at this temperature for 10 minutes before being warmed to 40° C. for 2 hours. The cooled reaction mixture was then diluted with water (20 mL) and ethyl acetate (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, concentrated in vacuo, and purified flash chromatography (silica, 4 g, ISCO, 0-65% ethyl acetate in heptane) to afford the title compound as a colorless oil, which was used in the next step without any further purification (60 mg, 70%).

Workup

  1. additionwas added in one portion
  2. customThe cooled reaction mixture
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified flash chromatography (silica, 4 g, ISCO, 0-65% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-8e346c3f822b45db97aa39421cbe789f
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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