Ammonia → 5-chloro-3-(2,6-difluoro-pyridin-3-ylmethyl)-1H-pyrrolo[2,3-b]pyridine

HRID 1754725Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[N:3]=1.C([Li])CCC.C([Cu])#N.C(OC([N:24]1[C:28]2=[N:29][CH:30]=[C:31]([Cl:33])[CH:32]=[C:27]2[C:26]([CH2:34]Cl)=[CH:25]1)=O)(C)(C)C.N>O1CCCC1.CCCCCC.O>[Cl:33][C:31]1[CH:32]=[C:27]2[C:26]([CH2:34][C:7]3[C:2]([F:1])=[N:3][C:4]([F:8])=[CH:5][CH:6]=3)=[CH:25][NH:24][C:28]2=[N:29][CH:30]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To 2,6-Difluoropyridine (58, 3.40 g, 0.0295 mol) in tetrahydrofuran (200.0 mL), under an atmosphere of nitrogen at −78° C., 2.50 M of n-butyllithium in hexane (12.0 mL) was added slowly. After 60 minutes, CuCN.2LiCl (0.75 M in tetrahydrofuran, 40.0 mL) was added to the reaction mixture. After 5 minutes, 5-chloro-3-chloromethyl-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester (535, 4.20 g, 0.0139 mol, prepared as described in Example 49, Scheme 164) in tetrahydrofuran (20 mL) was added to the reaction. The reaction was stirred at −78° C. overnight, then poured into water and ammonia (10 mL), and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 15% ethyl acetate in hexane to give a white solid (P-0155, 300 mg, 7.7%). MS (ESI) [M−H+]−=278.1.

Workup

waitAfter 5 minutes
extractionextracted with ethyl acetate
dry with materialThe organic layer was dried over anhydrous sodium sulfate
filtrationfiltered
concentrationThe filtrate was concentrated
custompurified by silica gel column chromatography
washeluting with 15% ethyl acetate in hexane
customto give a white solid (P-0155, 300 mg, 7.7%)

Sources & evidence

ORD record: ord-9e2351fa3e7242439e4c4527d46af6de
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169250B2

Reaction notes

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