Potassium Phosphate, Tribasic → HCID 53373964, compound

HRID 335819Notes

Reaction equation

HRID 335819 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[O:8][C:9]3[C:14]([C@@:15]4([CH2:19][O:18][C:17]([NH2:20])=[N:16]4)[C:4]=2[CH:3]=1)=[CH:13][C:12]([C:21]1[C:22]([F:28])=[N:23][CH:24]=[CH:25][C:26]=1[F:27])=[CH:11][CH:10]=3.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[O:37]1[CH2:42][CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH2:39][CH2:38]1>O1CCOCC1.O.CCOC(C)=O.C([O-])([O-])=O.[Na+].[Na+]>[F:28][C:22]1[C:21]([C:12]2[CH:13]=[C:14]3[C@@:15]4([CH2:19][O:18][C:17]([NH2:20])=[N:16]4)[C:4]4[CH:3]=[C:2]([C:40]5[CH2:41][CH2:42][O:37][CH2:38][CH:39]=5)[N:7]=[CH:6][C:5]=4[O:8][C:9]3=[CH:10][CH:11]=2)=[C:26]([F:27])[CH:25]=[CH:24][N:23]=1

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 86658465HCID 86658465, compound

Product 1

HCID 53373964HCID 53373964, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A glass microwave reaction vessel was charged with (S)-3-chloro-7-(2,4-difluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-oxazol]-2′-amine (0.190 g, 0.474 mmol), potassium phosphate (0.302 g, 1.422 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.169 g, 0.806 mmol) and bis(di-tert-butylphenylphosphine)dichloropalladium (II) (0.029 g, 0.047 mmol) in dioxane (4 mL) and water (1.2 mL). The reaction mixture was heated in microwave at 110° C. for 30 min. The mixture was diluted with EtOAc and saturated Na2CO3. The organic layer was washed twice with saturated Na2CO3, dried over Na2SO4 and concentrated in vacuo. The crude residue was purified by silica gel chromatography (2-10% MeOH—CH2Cl2) to provide a residue that was purified by HPLC to provide the titled compound as a white solid. MS m/z=449.2 [M+H]+. Calculated for C24H18F2N4O3: 448.13.

Workup

  1. customA glass microwave reaction vessel
  2. washThe organic layer was washed twice with saturated Na2CO3
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude residue was purified by silica gel chromatography (2-10% MeOH—CH2Cl2)
  6. customto provide a residue that
  7. customwas purified by HPLC

Sources & evidence

ORD record
ord-a537a04d38724a61b78054efa7f426f0
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

Loading…