Potassium Phosphate, Tribasic → 2-(5-Fluoropyridin-3-yl)-3-methylpyrazolo[1,5-a]pyridine

HRID 530037Notes

Reaction equation

HRID 530037 reaction equation
Cl[C:2]1[C:10]([CH3:11])=[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[F:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[N:17][CH:18]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:12][C:13]1[CH:14]=[C:15]([C:2]2[C:10]([CH3:11])=[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][N:4]3[N:3]=2)[CH:16]=[N:17][CH:18]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 44717403(5-Fluoropyridin-3-yl)boronic acidHCID 717433412-Chloro-3-methylpyrazolo[1,5-A]pyridine

Product 1

HCID 894634532-(5-Fluoropyridin-3-yl)-3-methylpyrazolo[1,5-a]pyridine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A solution 2-chloro-3-methylpyrazolo[1,5-a]pyridine (38-1; 0.15 g, 0.9 mmol), (5-fluoropyridin-3-yl)boronic acid (0.15 g, 1.05 mmol), and potassium phosphate tribasic (0.574 g, 2.7 mmol) in tetrahydrofuran (10 mL) was degassed for 10 min. Then 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (0.074 g, 0.18 mmol) and palladium acetate (0.02 g, 0.09 mmol) were added and heated in a sealed tube at 100° C. for 18 h. The reaction mixture was then cooled to room temperature, filtered and concentrated under reduced pressure. Purification of the resulting residue by prep HPLC (Analytical Conditions: Column: XTERRA C18 (250 mm×4.6 mm×5 μm) mobile phase(A):0.01% ammonia in water, mobile phase (B): acetonitrile flow rate: 1.0 mL/min time/% B: 0/20, 8/50, 25/50, 26/20, 30/20) provided 2-(5-fluoropyridin-3-yl)-3-methylpyrazolo[1,5-a]pyridine. 1H NMR (400 MHz, DMSO-d6) δ 8.88 (s, 1 H), 8.67-8.65 (d, J=8.0 Hz, 1 H), 8.06-8.03 (d, J=12 Hz, 1 H), 7.73-7.71 (d, J=8.0 Hz, 1 H), 7.23-7.20 (t, J=4.0 Hz, 1 H), 6.92-6.89 (t, J=4.0 Hz, 1 H), 2.45 (s, 3 H). MS (M+1): 228.0.

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. filtrationfiltered
  3. concentrationconcentrated under reduced pressure
  4. customPurification of the resulting residue by prep HPLC (Analytical Conditions: Column: XTERRA C18 (250 mm×4.6 mm×5 μm) mobile phase(A):0.01% ammonia in water, mobile phase (B): acetonitrile flow rate: 1.0 mL/min time/% B: 0/20, 8/50, 25/50, 26/20, 30/20)

Sources & evidence

ORD record
ord-39b6dc0085c34128a3efbc49e0304295
Source dataset
uspto-grants-2016_05
Patent number
US09351973B2

Reaction notes

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