5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine → 5-(7-chloro-2,2-difluoro-3H-benzo[3,4-e]1,4-dioxin-6-yl)-2-pyridylamine

HRID 1036154Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][N:3]=1.Br[C:18]1[C:29]([Cl:30])=[CH:28][C:21]2[O:22][C:23]([F:27])([F:26])[CH2:24][O:25][C:20]=2[CH:19]=1>O1CCOCC1.CC#N.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>[Cl:30][C:29]1[C:18]([C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[N:3][CH:4]=2)=[CH:19][C:20]2[O:25][CH2:24][C:23]([F:27])([F:26])[O:22][C:21]=2[CH:28]=1

Participants

Conditions

Temperature: 85 °C

Procedure

2-Aminopyridine-5-boronic acid pinacol ester (62 mg, 0.28 mmol) and 254 (67 mg, 0.23 mmol) were dissolved in 2 mL 1,4-dioxane and 2 mL MeCN. Next 1 ml of 2 M K3PO3 was added and the mixture was bubbled with Ar for 2 min before bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (A-Phos, 14 mg, 0.02 mmol) was added. The reaction was then heated at 85° C. for 2 h. The reaction was cooled and the mixture worked-up with a EtOAc extraction. The resulting crude product was purified by flash column and afforded 255 (6 mg, 9%) as yellow solid.

Workup

additionwas added
temperatureThe reaction was cooled
extractionthe mixture worked-up with a EtOAc extraction
customThe resulting crude product was purified by flash column

Sources & evidence

ORD record: ord-8b04ecabea4144728476939bc02f6638
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546403B2

Reaction notes

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