Sodium Iodide → 1-(2,3-Difluoro-4-hydroxyphenyl)-2-(3,5-dimethylisoxazol-4-yl)-1H-indole-3-carbonitrile

HRID 383454Notes

Reaction equation

Br[C:2]1[N:3]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[C:15]([F:20])[C:14]=2[F:21])[C:4]2[C:9]([C:10]=1[C:11]#[N:12])=[CH:8][CH:7]=[CH:6][CH:5]=2.[CH3:22][C:23]1[C:27](B(O)O)=[C:26]([CH3:31])[O:25][N:24]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC.O>[F:21][C:14]1[C:15]([F:20])=[C:16]([OH:19])[CH:17]=[CH:18][C:13]=1[N:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:10]([C:11]#[N:12])=[C:2]1[C:27]1[C:23]([CH3:22])=[N:24][O:25][C:26]=1[CH3:31]

Participants

Conditions

Temperature: 150 °C

Procedure

To 2-bromo-1-(2,3-difluoro-4-hydroxyphenyl)-1H-indole-3-carbonitrile (Example 103) was added 1.5 eq 3,5-dimethylisooxazole-4-boronic acid, 4 eq potassium carbonate, 2 eq sodium iodide and 10 mol % tetrakis(triphenylphosphine)palladium. DME:H2O (1:1) was added and the vial was flushed with nitrogen, sealed and stirred at 150° C. for 10 min. The reaction mixture was cooled to rt, diluted with H2O and extracted with DCM. The organic phase was evaporated to dryness and purified on silica column using 1:1 n-heptane:EtOAc as mobile phase. ES/MS m/z: 366.20 (M+H), 364.20 (M−H); 1H NMR (CDCl3, 500 MHz): 7.84 (d, 1H), 7.39 (m, 2H), 7.19 (d, 1H), 6.93 (broad m, 2H), 2.42 (s, 1.5H), 2.24 (s, 1.5H), 2.19 (s, 1.5H), 2.01 (s, 1.5H)

Workup

customthe vial was flushed with nitrogen
customsealed
temperatureThe reaction mixture was cooled to rt
additiondiluted with H2O
extractionextracted with DCM
customThe organic phase was evaporated to dryness
custompurified on silica column

Sources & evidence

ORD record: ord-adc07b403bb247d9a2f8668c70ee4ee6
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367665B2

Reaction notes

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