4-(Piperidin-1-ylmethyl)phenylboronic acid hydrobromide → 6'-Methoxy-2-fluoro-5-(4-piperidin-1-ylmethyl-phenyl)-[3,4']bipyridinyl-3'-ylamine

HRID 1888565Notes

Reaction equation

HRID 1888565 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH2:9])=[C:5]([C:10]2[C:11]([F:16])=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:4]=1.Br.[N:18]1([CH2:24][C:25]2[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=2)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>[F-].[K+].C(#N)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH2:9])=[C:5]([C:10]2[C:11]([F:16])=[N:12][CH:13]=[C:14]([C:28]3[CH:27]=[CH:26][C:25]([CH2:24][N:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)=[CH:30][CH:29]=3)[CH:15]=2)[CH:4]=1

Participants

7

Reactant 2

HCID 670275164-(Piperidin-1-ylmethyl)phenylboronic acid hydrobromideHCID 866534976'-Methoxy-2-fluoro-[3,4]bipyridinyl-3'-ylamine

Product 1

HCID 582668416'-Methoxy-2-fluoro-5-(4-piperidin-1-ylmethyl-phenyl)-[3,4']bipyridinyl-3'-ylamineYield 77%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 522689Potassium FluorideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6′-methoxy-2-fluoro-[3,4′]bipyridinyl-3′-ylamine (1.0 g, 3.4 mmol), 4-(piperidin-1-ylmethyl)phenylboronic acid hydrobromide (1.7 g, 5.7 mmol), and bis(triphenylphosphine)palladium(II) dichloride (0.18 g, 0.25 mmol) in 1N aqueous potassium fluoride (8.4 mL) and acetonitrile (12 mL) was heated under microwave irradiation at 100° C. for 25 minutes. The cooled reaction was diluted with water (100 mL) and extracted with DCM (3×50 mL). The combined organic layer was, dried over sodium sulfate, filtered, and purified by flash chromotagraphy (silica, 25 g column, Biotage, 0-10% methanol in (DCM containing 1% 2M ammonia in methanol)) to afford the title compound as a yellow/orange solid (1.0 g, 77%). 1H NMR (DMSO-D6, 500 MHz): 8.59 (s, 1H), 8.22 (d, J=8.0 Hz, 1H), 7.74 (s, 3H), 7.42 (s, 2H), 6.65 (s, 1H), 4.71 (s, 2H), 3.77 (s, 3H), 3.47 (s, 2H), 2.34 (s, 4H), 1.51 (s, 4H), 1.40 (s, 2H).

Workup

  1. customThe cooled reaction
  2. extractionextracted with DCM (3×50 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. custompurified by flash chromotagraphy (silica, 25 g column, Biotage, 0-10% methanol in (DCM containing 1% 2M ammonia in methanol))

Sources & evidence

ORD record
ord-445e8511333841e881be415ff1cd2188
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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