Potassium Phosphate, Tribasic → tert-butyl 4-(6-(6-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate

HRID 1431186Notes

Reaction equation

HRID 1431186 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.C([O:33][CH2:34][C:35]1[C:40](B2OC(C)(C)C(C)(C)O2)=[CH:39][CH:38]=[CH:37][C:36]=1[N:50]1[N:59]=[CH:58][C:57]2[C:52](=[C:53]([F:64])[CH:54]=[C:55]([C:60]([CH3:63])([CH3:62])[CH3:61])[CH:56]=2)[C:51]1=[O:65])(=O)C.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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]>[C:60]([C:55]1[CH:56]=[C:57]2[C:52](=[C:53]([F:64])[CH:54]=1)[C:51](=[O:65])[N:50]([C:36]1[C:35]([CH2:34][OH:33])=[C:40]([C:2]3[CH:3]=[C:4]([NH:10][C:11]4[N:16]=[CH:15][C:14]([CH:17]5[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]5)=[CH:13][CH:12]=4)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=3)[CH:39]=[CH:38][CH:37]=1)[N:59]=[CH:58]2)([CH3:63])([CH3:61])[CH3:62]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 594737692-(6-(tert-Butyl)-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetateHCID 66742247Tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate

Product 1

HCID 66742289tert-butyl 4-(6-(6-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

This reaction was carried out under similar conditions to those described above in step 7 of the preparation of Example 6. A solution of tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate (150 mg, 357 μmol), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate (177 mg, 357 μmol), xPhos (17 mg, 35.7 μmol) and potassium phosphate (190 mg, 893 mol) in 10 ml of dioxane/water (9:1) was degassed with nitrogen for 10 minutes and bis(dibenzylideneacetone)palladium (0) (10.3, 17.9 μmol) was added.

Workup

  1. customthose described above in step 7 of the preparation of Example 6

Sources & evidence

ORD record
ord-4df7ed717f4c4897a0268b243d50b5f2
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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