(6-Methoxypyridin-3-yl)boronic acid → HCID 67298192, compound

HRID 1520326Notes

Reaction equation

HRID 1520326 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)[N:6]=[C:5]2[NH:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[C:21]([Cl:26])[CH:20]=1.[CH3:27][O:28][C:29]1[N:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.O>[Cl:26][C:21]1[CH:20]=[C:19]([NH:18][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:32]4[CH:33]=[N:34][C:29]([O:28][CH3:27])=[CH:30][CH:31]=4)[CH:3]=3)[N:8]=[C:7]([C:12]3[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=3)[N:6]=2)[CH:24]=[CH:23][C:22]=1[F:25]

Participants

6

Reactant 3

HCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 67298005HCID 67298005, compound

Product 1

HCID 67298192HCID 67298192, compoundYield 54.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

A 2.0 dram reaction vial was charged with 6-bromo-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (synthesized as described in Scheme 1 and 4, substituting 5-bromo-2-nitrobenzoic acid for 2-nitro-5-propoxy-benzoic acid and 3-chloro-4-fluoroaniline for 2-aminobenzamide) (100 mg, 0.233 mmol, 1.0 equiv), 6-methoxypyridin-3-ylboronic acid (44.5 mg, 0.291 mmol, 1.25 equiv), Pd(APhos)2Cl2 (6.6 mg, 0.0093 mmol, 4 mol %) and potassium phosphate monohydrate (69 mg, 0.70 mmol, 3.0 equiv). The mixture was suspended in dioxane/water (9:1, 4 mL), and the reaction was heated at 90° C. for 14 h. The reaction mixture was cooled to room temperature, diluted with water (15 mL) and the resultant precipitate was collected by filtration. The crude product was purified by stirring in methanol for 30 min at 60° C. to give the desired product as a pale yellow solid (58 mg, 54%) LCMS m/z=458.1 (M+1) (Method C) (retention time=2.56 min). 1H NMR (300 MHz, DMSO) δ 10.12 (s, 1H), 9.53 (s, 1H), 8.82 (s, 1H), 8.70 (dd, J=16.9, 5.4 Hz, 3H), 8.25 (d, J=8.6 Hz, 3H), 8.01-7.87 (m, 2H), 7.57 (dd, J=11.2, 6.0 Hz, 2H), 7.03 (d, J=8.6 Hz, 1H), 3.94 (s, 3H).

Workup

  1. customA 2.0 dram reaction
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationthe resultant precipitate was collected by filtration
  4. customThe crude product was purified

Sources & evidence

ORD record
ord-3aa5251a5f1e4f298d3d821102ad4327
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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