1,4-Dioxane → 2-fluoro-7-(2-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

HRID 335829Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:15]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:14]3[C:9](=[N:10][C:11]([F:21])=[CH:12][CH:13]=3)[O:8][C:5]2=[CH:6][CH:7]=1.[F:22][C:23]1[C:28](B(O)O)=[CH:27][CH:26]=[CH:25][N:24]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.O>[F:21][C:11]1[N:10]=[C:9]2[O:8][C:5]3[C:4]([C:15]4([CH2:19][O:18][C:17]([NH2:20])=[N:16]4)[C:14]2=[CH:13][CH:12]=1)=[CH:3][C:2]([C:28]1[C:23]([F:22])=[N:24][CH:25]=[CH:26][CH:27]=1)=[CH:7][CH:6]=3

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 7-bromo-2-fluoro-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (26.0 mg, 0.074 mmol), 2-fluoro-3-pyridineboronic acid (16.74 mg, 0.119 mmol), bis-(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(ii) (2.103 mg, 2.97 μmol) and potassium phosphate (47.3 mg, 0.223 mmol) in a 2:1 mixture of dioxane and water (1.5 ml) was heated at 110° C. in the microwave for 20 minutes. The reaction mixture was subjected to purification by silica gel chromatography (SiO2, CH2Cl2 to CH2Cl2/MeOH=100:1 to 100:6) to give 2-fluoro-7-(2-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as a white solid. MS m/z=367.0 [M+H].

Workup

customThe reaction mixture was subjected to purification by silica gel chromatography (SiO2, CH2Cl2 to CH2Cl2/MeOH=100:1 to 100:6)

Sources & evidence

ORD record: ord-b8823549ee4e4885b3edd532660898af
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883782B2

Reaction notes

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