Acetonitrile → HCID 71253911, compound

HRID 1774968Notes

Reaction equation

HRID 1774968 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([CH3:11])=[N:9][N:8]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[C:5]2=[CH:6][N:7]=1.[F:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[N:23][CH:24]=1.C(#N)C.C([O-])(=O)C.[K+]>O.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:18][C:19]1[CH:20]=[C:21]([C:2]2[CH:3]=[C:4]3[C:10]([CH3:11])=[N:9][N:8]([CH:12]4[CH2:17][CH2:16][CH2:15][CH2:14][O:13]4)[C:5]3=[CH:6][N:7]=2)[CH:22]=[N:23][CH:24]=1

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 517044Potassium AcetateHCID 44717403(5-Fluoropyridin-3-yl)boronic acidHCID 86676683HCID 86676683, compound

Product 1

HCID 71253911HCID 71253911, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 10340Sodium CarbonateSolvent

Procedure

To a mixture of 5-bromo-3-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine (90.0 mg, 0.304 mmol), 5-fluoropyridin-3-ylboronic acid (128.6 mg, 0.9124 mmol) and 1,1′-Bis(diphenylphosphino)ferrocenepalladium (II) chloride (37.2 mg, 0.0456 mmol) in Acetonitrile (2.86 mL, 54.7 mmol) was added 1.0 M of Potassium acetate in Water (0.456 mL) and 1.0 M of Sodium carbonate in Water (0.456 mL). The reaction mixture was irradiated in microwave at 125° C. for 20 min. The reaction was filtered thru celite and concentrated. The crude product was purified by silica gel column using ethyl acetate/heptane to give 5-(5-fluoropyridin-3-yl)-3-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine which was dissolved in 12M HCl (1.30 mL, 15.6 mmol) and Methanol (13.0 mL). The reaction mixture was stirred at RT (room temperature) for 18 h. The reaction was concentrated and then submitted for rHPLC to give 123 (27.9 mg, 40.2% yield). ESI MS m/z=229.1 (M+1). 1H NMR (400 MHz, DMSO) δ 9.25 (s, 1H), 9.08 (s, 1H), 8.62-8.49 (m, 2H), 8.47-8.30 (m, 1H), 2.60 (s, 3H)

Workup

  1. customThe reaction mixture was irradiated in microwave at 125° C. for 20 min
  2. filtrationThe reaction was filtered thru celite
  3. concentrationconcentrated
  4. customThe crude product was purified by silica gel column

Sources & evidence

ORD record
ord-9c85f9ef93304fcaae0db43a76a66817
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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