Water → 3'-((2-(2,6-difluorophenyl)imidazo[1,5-b]pyridazin-7-yl)amino)-3,4'-bipyridin-6(1 H)-one

HRID 716196Notes

Reaction equation

HRID 716196 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[NH:8][C:9]1[N:13]2[N:14]=[C:15]([C:18]3[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=3[F:25])[CH:16]=[CH:17][C:12]2=[CH:11][N:10]=1.[OH:26][C:27]1[N:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C([O-])([O-])=O.[Na+].[Na+].O>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>[F:25][C:19]1[CH:20]=[CH:21][CH:22]=[C:23]([F:24])[C:18]=1[C:15]1[CH:16]=[CH:17][C:12]2[N:13]([C:9]([NH:8][C:3]3[CH:4]=[N:5][CH:6]=[CH:7][C:2]=3[C:30]3[CH:29]=[CH:28][C:27](=[O:26])[NH:32][CH:31]=3)=[N:10][CH:11]=2)[N:14]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 70982735N-(4-chloro-3-pyridinyl)-2-(2,6-difluorophenyl)imidazo[1,5-b]pyridazin-7-amineHCID 178514836HCID 178514836, compound

Product 1

HCID 710072503'-((2-(2,6-difluorophenyl)imidazo[1,5-b]pyridazin-7-yl)amino)-3,4'-bipyridin-6(1 H)-oneYield 2.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A glass microwave reaction vessel was charged with N-(4-chloro-3-pyridinyl)-2-(2,6-difluorophenyl)imidazo[1,5-b]pyridazin-7-amine (Example 27, Step 1, 40 mg, 0.11 mmol), 6-hydroxypyridin-3-ylboronic acid (19 mg, 0.13 mmol, Combi-Blocks, Inc.), Pd(PPh3)4 (13 mg, 0.01 mmol) and 2 M Na2CO3 (aq., 0.17 mL, 0.34 mmol) in dioxane (1.00 mL). The reaction was stirred and heated in a microwave at 120° C. for 20 min. H2O was added and the mixture was extracted with EtOAc (3×). The combined organic layers were dried over anh. Na2SO4, filtered and concentrated. The crude material was purified by silica gel chromatography (0-5% MeOH in CH2Cl2) to provide 3′-((2-(2,6-difluorophenyl)imidazo[1,5-b]pyridazin-7-yl)amino)-3,4′-bipyridin-6(1 H)-one (1 mg, 2.40 μmol, 2% yield) as a yellow solid. MS (ESI, pos. ion) m/z: 416.9 (M+1). 1H NMR (400 MHz, MeOH-d4) δ ppm 8.82 (s, 1 H), 8.30 (d, J=5.09 Hz, 1 H), 7.96 (d, J=9.39 Hz, 1 H), 7.74 (dd, J=9.59, 2.54 Hz, 1 H), 7.55-7.64 (m, 2 H), 7.37 (d, J=5.09 Hz, 1 H), 7.24 (s, 1 H), 6.69 (d, J=9.39 Hz, 1 H), 6.44 (d, J=9.39 Hz, 1 H).

Workup

  1. customA glass microwave reaction vessel
  2. extractionthe mixture was extracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried over anh. Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by silica gel chromatography (0-5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-a591e69c9e064f56b8e2f418c3e8c9d3
Source dataset
uspto-grants-2015_11
Patent number
US09187486B2

Reaction notes

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