Potassium Phosphate, Tribasic → (2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(5-cyclopropyl-1-methyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate

HRID 407695Notes

Reaction equation

HRID 407695 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH:16]3[CH2:18][CH2:17]3)[N:13]([CH3:19])[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:20]([O:23][CH2:24][C:25]1[C:26]([N:40]2[N:49]=[CH:48][C:47]3[C:42](=[C:43]([F:54])[CH:44]=[C:45]([C:50]([CH3:53])([CH3:52])[CH3:51])[CH:46]=3)[C:41]2=[O:55])=[N:27][CH:28]=[CH:29][C:30]=1B1OC(C)(C)C(C)(C)O1)(=[O:22])[CH3:21].C([O-])(=O)C.[Na+].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(#N)C.O>[C:20]([O:23][CH2:24][C:25]1[C:26]([N:40]2[N:49]=[CH:48][C:47]3[C:42](=[C:43]([F:54])[CH:44]=[C:45]([C:50]([CH3:52])([CH3:51])[CH3:53])[CH:46]=3)[C:41]2=[O:55])=[N:27][CH:28]=[CH:29][C:30]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH:16]3[CH2:18][CH2:17]3)[N:13]([CH3:19])[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:22])[CH3:21]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866839715-Bromo-3-(5-cyclopropyl-1-methyl-1H-pyrazol-3-ylamino)-1-methylpyridine-2(1H)-oneHCID 86683972(2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate

Product 1

HCID 86683970(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(5-cyclopropyl-1-methyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl AcetateYield 26.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A sealed tube equipped with a magnetic stirrer was charged with 126f (200 mg, 0.62 mmol), (2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate 116c (268 mg, 0.65 mmol), Pd(dppf)Cl2 (18 mg, 0.025 mmol), sodium acetate (74 mg, 0.90 mmol), K3PO4 (191 mg, 0.90 mmol), and acetonitrile/water (5 mL/0.5 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 2.0 h. It was then cooled to room temperature and filtered. The filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 10:1 dichloromethane/methanol to afford 126g (100 mg, 26%) as a brown solid. MS-ESI: [M+H]+ 612.3.

Workup

  1. customA sealed tube equipped with a magnetic stirrer
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. customThe filtrate was evaporated under reduced pressure
  6. customThe residue was purified by silica-gel column chromatography
  7. washeluting with 10:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-bda3cae6bbce427e80f258676f680d50
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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