Potassium Carbonate → (6-Phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methanol

HRID 912070Notes

Reaction equation

Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][OH:12])=[N:9][N:10]=2)[N:7]=1.[C:13]1(B(O)O)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.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.O>[C:13]1([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([CH2:11][OH:12])=[N:9][N:10]=3)[N:7]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A suspension of (6-chloro[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methanol (0.289 mmol, 1 eq), phenylboronic acid (0.665 mmol, 2.3 eq), Pd(PPh3)4 (45.9 mg, 0.0405 mmol, 14 mol %), and K2CO3 (132 mg, 0.955 mmol, 3.3 eq) in a 4:1 ratio of dioxane (4 mL) to H2O (1 mL) was evacuated and charged with nitrogen several times. The reaction sample was then heated conventionally at 85° C. for 1 h. CH2Cl2 and H2O were added and a standard aqueous workup was performed. The crude material was purified by pTLC [Silicycle, 1000 μM, 20×20 plate], which required two developments in a 3% MeOH in EtOAc solvent system. 1H NMR (400 MHz, CDCl3): δ=1.69 (br s, 1H), 5.35 (s, 2H), 7.56-7.60 (m, 3H), 7.64 (d, J=9.6 Hz, 1H), 7.97-8.02 (m, 2H), 8.22 (d, J=9.6 Hz, 1H). MS (ES+): m/z 227.08 (100) [MH+]. HPLC: tR=2.42 min (ZQ3, polar—5 min).

Workup

customwas evacuated
additioncharged with nitrogen several times
additionCH2Cl2 and H2O were added
customThe crude material was purified by pTLC [Silicycle, 1000 μM, 20×20 plate], which
custom5 min

Sources & evidence

ORD record: ord-5a9fcf126e674068a1cbb3236f65032f
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08022206B2

Reaction notes

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