1,4-Dioxane → (S)-3-(3,6-dihydro-2H-pyran-4-yl)-7-(2-fluoropyridin-3-yl)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine

HRID 455638Notes

Reaction equation

HRID 455638 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[O:8][C:9]3[C:14]([C@:15]4([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]4)[C:4]=2[CH:3]=1)=[CH:13][C:12]([C:22]1[C:23]([F:28])=[N:24][CH:25]=[CH:26][CH:27]=1)=[CH:11][CH:10]=3.[O:29]1[CH2:34][CH:33]=[C:32](B(O)O)[CH2:31][CH2:30]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[O:29]1[CH2:30][CH:31]=[C:32]([C:2]2[N:7]=[CH:6][C:5]3[O:8][C:9]4[C:14]([C@:15]5([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]5)[C:4]=3[CH:3]=2)=[CH:13][C:12]([C:22]2[C:23]([F:28])=[N:24][CH:25]=[CH:26][CH:27]=2)=[CH:11][CH:10]=4)[CH2:33][CH2:34]1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 235936383,6-Dihydro-2H-pyran-4-ylboronic acidHCID 86658381(S)-3-chloro-7-(2-fluoropyridin-3-yl)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine

Product 1

HCID 67438959(S)-3-(3,6-dihydro-2H-pyran-4-yl)-7-(2-fluoropyridin-3-yl)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amineYield 92.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A vial was charged with and (S)-3-chloro-7-(2-fluoropyridin-3-yl)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (79.05 mg, 0.199 mmol), 3,6-dihydro-2H-pyran-4-ylboronic acid (76 mg, 0.598 mmol), bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (7.05 mg, 9.96 μmol), and potassium phosphate (127 mg, 0.598 mmol). Dioxane (747 μL) and water (249 μL) were added, and the vial was sealed and heated in a Biotage Initiator microwave reactor for 30 min at 110° C. The mixture was extracted with EtOAc (3×), and the combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (0-10% MeOH/DCM) to give (S)-3-(3,6-dihydro-2H-pyran-4-yl)-7-(2-fluoropyridin-3-yl)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (82.18 mg) as a yellow solid.

Workup

  1. customthe vial was sealed
  2. extractionThe mixture was extracted with EtOAc (3×)
  3. concentrationthe combined organic extracts were concentrated
  4. customThe residue was purified by chromatography on silica gel (0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-9578019111954b0ba1184404898b9094
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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