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

HRID 60319Notes

Reaction equation

Br[C:2]1[N:10]=[CH:9][C:8]2[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:6]3[N:19]=[CH:20][CH:21]=[C:22]([O:23][C@@H:24]4[CH2:29][CH2:28][CH2:27][N:26]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:25]4)[C:5]=3[C:4]=2[CH:3]=1.[CH3:37][N:38]1[CH:42]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH:40]=[N:39]1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[CH3:37][N:38]1[CH:42]=[C:41]([C:2]2[N:10]=[CH:9][C:8]3[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:17])([CH3:18])[CH3:16])[C:6]4[N:19]=[CH:20][CH:21]=[C:22]([O:23][C@@H:24]5[CH2:29][CH2:28][CH2:27][N:26]([C:30]([O:32][C:33]([CH3:35])([CH3:36])[CH3:34])=[O:31])[CH2:25]5)[C:5]=4[C:4]=3[CH:3]=2)[CH:40]=[N:39]1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of (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 (50 mg, 0.09 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (90 mg, 0.43 mmol), 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (6.3 mg, 0.009 mmol), and saturated aqueous sodium carbonate solution (0.1 mL) in acetonitrile (0.9 mL) was heated under microwave irradiation at 130° C. for 30 minutes. The reaction mixture was concentrated in vacuo, and purified flash chromatography (silica, 4 g, ISCO, 0-90% ethyl acetate in heptane) to afford the title compound as a light brown oil, which was used in the next step without any further purification (50 mg).

Workup

concentrationThe reaction mixture was concentrated in vacuo
custompurified flash chromatography (silica, 4 g, ISCO, 0-90% ethyl acetate in heptane)

Sources & evidence

ORD record: ord-e3b036c6250c4fe3b68ef61c84e5842b
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440976B2

Reaction notes

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