Potassium Phosphate, Tribasic → HCID 86689263, compound

HRID 1409523Notes

Reaction equation

HRID 1409523 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[O:13][C:7]1[CH:8]=[N:9][C:10]([Cl:12])=[CH:11][C:6]=1[C:5]12[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[O:19][C:18]([NH2:26])=[N:17]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[F:35][C:36]1[C:41](B(O)O)=[CH:40][CH:39]=[CH:38][N:37]=1>O.O1CCOCC1.O>[Cl:12][C:10]1[N:9]=[CH:8][C:7]2[O:13][C:14]3[C:4]([C:5]4([C:21]5[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=5[O:19][C:18]([NH2:26])=[N:17]4)[C:6]=2[CH:11]=1)=[CH:3][C:2]([C:41]1[C:36]([F:35])=[N:37][CH:38]=[CH:39][CH:40]=1)=[CH:16][CH:15]=3

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27832702-Fluoropyridine-3-boronic acidHCID 86689262HCID 86689262, compound

Product 1

HCID 86689263HCID 86689263, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A microwave tube was charged with 7′-bromo-3′-chlorospiro[benzo[e][1,3]oxazine-4,5′-chromeno[2,3-c]pyridin]-2-amine (0.135 g, 0.315 mmol), potassium phosphate tribasic (0.078 mL, 0.945 mmol), 2-fluoro-3-pyridineboronic acid (0.049 g, 0.346 mmol) in dioxane water (3 mL, 1:1). The reaction mixture was heated in microwave at 100° C. for 40 min. The mixture was diluted with water and extracted with EtOAc. The organic layer was washed with saturated sodium bicarbonate solution twice, then dried on sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by column chromatography with gradient of 20-100% EtOAc/Hexane to give 3′-chloro-7′-(2-fluoropyridin-3-yl)spiro[benzo[e][1,3]oxazine-4,5′-chromeno[2,3-c]pyridin]-2-amine. This material (0.049 g, 0.110 mmol) was combined with potassium phosphate tribasic (0.027 mL, 0.330 mmol), 5,6-dihydro-2H-pyran-3-ylboronic acid (0.028 g, 0.220 mmol) and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (3.90 mg, 5.51 μmol) in dioxane/water (1 mL, 3:1). The mixture was heated to 100° C. for 1 h. The reaction was completed and it was poured into water and extracted with EtOAc three times. The combined organic layers were washed with brine, dried on sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography with gradient of 70-100% EtOAc/Hexane to give the desired product. MS m/z=493.1 [M+H]+.

Workup

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with saturated sodium bicarbonate solution twice
  3. customdried on sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by column chromatography with gradient of 20-100% EtOAc/Hexane

Sources & evidence

ORD record
ord-7ac2900f66af44628f3ba002de2e5282
Source dataset
uspto-grants-2014_12
Patent number
US08921363B2

Reaction notes

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