Potassium Phosphate, Tribasic → Acetic acid 2-{5-[5-(1-amino-1-methyl-ethyl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl}-6-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-benzyl ester

HRID 2069865Notes

Reaction equation

HRID 2069865 reaction equation
[NH2:1][C:2]([C:5]1[CH:6]=[CH:7][C:8]([NH:11][C:12]2[C:13](=[O:20])[N:14]([CH3:19])[CH:15]=[C:16](Br)[CH:17]=2)=[N:9][CH:10]=1)([CH3:4])[CH3:3].[C:21]([C:25]1[CH:26]=[C:27]2[C:32](=[C:33]([F:35])[CH:34]=1)[C:31](=[O:36])[N:30]([C:37]1[CH:47]=[CH:46][CH:45]=[C:44](B3OC(C)(C)C(C)(C)O3)[C:38]=1[CH2:39][O:40][C:41](=[O:43])[CH3:42])[N:29]=[CH:28]2)([CH3:24])([CH3:23])[CH3:22].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]>[NH2:1][C:2]([C:5]1[CH:6]=[CH:7][C:8]([NH:11][C:12]2[C:13](=[O:20])[N:14]([CH3:19])[CH:15]=[C:16]([C:44]3[CH:45]=[CH:46][CH:47]=[C:37]([N:30]4[N:29]=[CH:28][C:27]5[C:32](=[C:33]([F:35])[CH:34]=[C:25]([C:21]([CH3:23])([CH3:22])[CH3:24])[CH:26]=5)[C:31]4=[O:36])[C:38]=3[CH2:39][O:40][C:41](=[O:43])[CH3:42])[CH:17]=2)=[N:9][CH:10]=1)([CH3:4])[CH3:3]

Participants

8

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 594738243-[5-(1-Amino-1-methyl-ethyl)-pyridin-2-ylamino]-5-bromo-1-methyl-1H-pyridin-2-one

Product 1

HCID 59473787Acetic acid 2-{5-[5-(1-amino-1-methyl-ethyl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl}-6-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-benzyl esterYield 54%

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

3-[5-(1-Amino-1-methyl-ethyl)-pyridin-2-ylamino]-5-bromo-1-methyl-1H-pyridin-2-one (160 mg, 0.474 mmol), Acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl ester (235 mg, 0.474 mmol), x-phos (34 mg, 0.0712 mmol), potassium phosphate (252 mg, 1.186 mmol) were dissolved in dioxane (4 ml) and water (1 ml). Finally bis(dibenzylideneacetone)palladium (41 mg, 0.0712 mmol) was added and heated in the microwave to 125° C. for 30 min. The reaction mixture was filtered, washed with dioxane, partially concentrated and dry loaded to a 24 g SiOH column. Purification by chromatography with 0-10% MeOH (contains 1% NH4OH) in DCM for 30 min afforded Acetic acid 2-{5-[5-(1-amino-1-methyl-ethyl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl}-6-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-benzyl ester (159 mg, 54%) as a yellow solid. MS (H+) 625.2.

Workup

  1. filtrationThe reaction mixture was filtered
  2. washwashed with dioxane
  3. concentrationpartially concentrated
  4. customdry
  5. customPurification by chromatography with 0-10% MeOH (contains 1% NH4OH) in DCM for 30 min

Sources & evidence

ORD record
ord-b8b318cef5ac40c79e128ab0c4a919cf
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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