Hydrochloric Acid → 3-Benzyl-N-(4-methylthiazol-2-yl)pyridin-2-amine hydrochloride

HRID 335098Notes

Reaction equation

Br[C:2]1[C:3]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH3:14])[N:13]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:21](B1C2CCCC1CCC2)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[ClH:37]>Cl[Pd]Cl.O.CN(C=O)C>[ClH:37].[CH2:21]([C:2]1[C:3]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH3:14])[N:13]=2)=[N:4][CH:5]=[CH:6][CH:7]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of mL 3-bromo-N-(4-methylthiazol-2-yl)pyridin-2-amine (70 mg, 0.26 mmol), Cs2CO3 (250 mg, 0.78 mmol), PdCl2 (dppf) (21.2 mg, 0.026 mmol), and DMF (2 mL) and water (0.5 mL) was purged with nitrogen and 9-benzyl-9-bora-bicyclo[3.3.1]nonane (1.5 mL, 0.78 mmol) was added and heated to 60° C. overnight. Additional 9-benzyl-9-bora-bicyclo[3.3.1]nonane (1.5 mL, 0.78 mmol) was added and heated again overnight. Poured into water and extracted with ether. The organic layer was dried with sodium sulfate, filtered and concentrated. The residue was purified on silica gel (10% EtOAc in hexanes) to afford the title compound (41.7 mg, 50.6% yield) as a white solid after HCl salt formation. 1H NMR (d6-DMSO) δ 8.30 (d, 1H), 7.62 (d, 1H), 7.35-7.10 (m, 6H), 6.82 (s, 1H), 4.21 (s, 2H), 2.32 (s, 3H); Mass spectrum (esi) m/z=282.2 (100)(M+H—HCl).

Workup

additionwas added
temperatureheated again overnight
extractionextracted with ether
dry with materialThe organic layer was dried with sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was purified on silica gel (10% EtOAc in hexanes)

Sources & evidence

ORD record: ord-fc5b9c53bfaf4c6fb555cbf601b51658
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883828B2

Reaction notes

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