Potassium Carbonate → 3-Bromo-7-(2-fluoropyridin-3-yl)-2',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,3'-[1,4]oxazin]-5'-amine

HRID 455632Notes

Reaction equation

[F:1][C:2]1[C:7](B(O)O)=[CH:6][CH:5]=[CH:4][N:3]=1.[Br:11][C:12]1[CH:13]=[C:14]2[C@@:25]3([N:30]=[C:29]([NH2:31])[CH2:28][O:27][CH2:26]3)[C:24]3[C:19](=[CH:20][CH:21]=[C:22](I)[CH:23]=3)[O:18][C:15]2=[N:16][CH:17]=1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O>[Br:11][C:12]1[CH:13]=[C:14]2[C:25]3([N:30]=[C:29]([NH2:31])[CH2:28][O:27][CH2:26]3)[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([C:7]4[C:2]([F:1])=[N:3][CH:4]=[CH:5][CH:6]=4)[CH:23]=3)[O:18][C:15]2=[N:16][CH:17]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A vial charged with 2-fluoropyridin-3-ylboronic acid (0.078 g, 0.556 mmol), PdCl2(dppf)-CH2Cl2 (0.022 g, 0.026 mmol), (S)-3-bromo-7-iodo-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-5′-amine, and potassium carbonate (0.293 g, 2.118 mmol) was treated with 2.5 mL dioxane and 1 mL water. The vial was then flushed with argon, sealed and heated to 80° C. for 1 hr. The reaction mixture was diluted with EtOAc, dried over MgSO4 and concentrated under reduced pressure to yield 3-bromo-7-(2-fluoropyridin-3-yl)-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.309 g, 0.700 mmol, 132% yield). This material was used without further purification.

Workup

customThe vial was then flushed with argon
customsealed
additionThe reaction mixture was diluted with EtOAc
dry with materialdried over MgSO4
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-eaebc7a40eb349cfbc7bf4a333a93a95
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08497264B2

Reaction notes

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