Water → 5-(6-chloro-3-methylpyridin-2-yl)-1-methyl-1H-indazole

HRID 879560Notes

Reaction equation

[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7](B(O)O)=[CH:8][CH:9]=2)[CH:4]=[N:3]1.Br[C:15]1[C:20]([CH3:21])=[CH:19][CH:18]=[C:17]([Cl:22])[N:16]=1.O.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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>[Cl:22][C:17]1[N:16]=[C:15]([C:7]2[CH:6]=[C:5]3[C:10](=[CH:9][CH:8]=2)[N:2]([CH3:1])[N:3]=[CH:4]3)[C:20]([CH3:21])=[CH:19][CH:18]=1

Participants

Conditions

Temperature: 110 °C

Procedure

In a 10 mL reaction vial, the 1-methyl-1H-indazol-5-ylboronic acid (500 mg, 2.84 mmol) and the 2-bromo-6-chloro-3-methylpyridine (585 mg, 2.84 mmol) were dissolved in dioxane (7 mL) and water (1.7 mL) under argon atmosphere. The mixture was bubbled with argon for 5 min. Then potassium carbonate (979 mg, 7.1 mmol) and Pd(PPh3)4 (49 3 mg, 0.428 mmol) were added sequentially. The resulting reaction mixture was then sealed and heated in oil bath at 110° C. for 2.5 h. Reaction was then partitioned between EtOAc (30 mL) and water (30 mL).The organic phase was washed with water (3×20 mL) and was concentrated. Residue was purified on silica gel column with 0-50% EtOAc/Hex to afford the title compound. LCMS-ESI+: calc'd for: C14H12ClN3: 258.1 and 260.1 (M+H+); found: 258.0 and 260.0 (M+H+).

Workup

customIn a 10 mL reaction vial
customThe mixture was bubbled with argon for 5 min
customThe resulting reaction mixture
customwas then sealed
customReaction
customwas then partitioned between EtOAc (30 mL) and water (30 mL).The organic phase
washwas washed with water (3×20 mL)
concentrationwas concentrated
customResidue was purified on silica gel column with 0-50% EtOAc/Hex

Sources & evidence

ORD record: ord-b5c872eeb1ad4bcfadee83c0d521edbd
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987250B2

Reaction notes

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