Potassium Phosphate, Tribasic → HCID 71534335, compound

HRID 1755431Notes

Reaction equation

HRID 1755431 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[N:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[N:7]=1.CC1(C)C(C)(C)OB([C:30]2[CH:31]=[C:32]([CH:38]=[CH:39][CH:40]=2)[C:33]([O:35][CH2:36][CH3:37])=[O:34])O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.O1CCOCC1>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([NH:11][C:4]2[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[N:7]=[C:2]([C:30]3[CH:31]=[C:32]([CH:38]=[CH:39][CH:40]=3)[C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH:3]=2)=[N:13][C:14]=1[O:20][CH3:21]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2773966Ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 71534334HCID 71534334, compound

Product 1

HCID 71534335HCID 71534335, compoundYield 34%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

6-Chloro-N-(5,6-dimethoxypyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (611 mg, 2 mmol), ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (828 mg, 3.00 mmol), potassium phosphate (1.06 g, 5.00 mmol) and X-phos (381 mg, 800 μmol) were combined with dioxane (29.4 ml) and water (2.94 ml) to give a light yellow suspension. The mixture was evacuated and back-filled with argon three times, then Pd2(dba)3 (183 mg, 200 μmol) was added and the mixture heated to 125° C. in a microwave for 60 min. The mixture was filtered and the filtrate concentrated. The residue was purified by chromatography (silica, 160 g, 20% to 50% EtOAc in hexanes, gradient over 20 min) to give ethyl 3-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (284 mg, 677 μmol, 34%) as an off-white powder. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 8.55-8.68 (m, 2H) 8.20 (dd, J=13.79, 7.74 Hz, 2H) 7.96 (d, J=1.51 Hz, 1H) 7.52-7.71 (m, 2H) 7.19 (d, J=8.31 Hz, 1H) 6.73 (d, J=8.31 Hz, 1H) 4.45 (q, J=7.18 Hz, 2H) 4.20 (s, 3H) 3.82-3.97 (m, 3H) 1.44 (t, J=7.18 Hz, 3H); LC/MS: 420.2 [MH]+.

Workup

  1. customto give a light yellow suspension
  2. customThe mixture was evacuated
  3. additionback-filled with argon three times
  4. filtrationThe mixture was filtered
  5. concentrationthe filtrate concentrated
  6. customThe residue was purified by chromatography (silica, 160 g, 20% to 50% EtOAc in hexanes, gradient over 20 min)

Sources & evidence

ORD record
ord-dbf6c87f255f48bdad7db858626a0b40
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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