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

HRID 1185237Notes

Reaction equation

HRID 1185237 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[N:15][CH:14]=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:17]([O:20][CH2:21][C:22]1[C:23]([N:37]2[N:46]=[CH:45][C:44]3[C:39](=[C:40]([F:51])[CH:41]=[C:42]([C:47]([CH3:50])([CH3:49])[CH3:48])[CH:43]=3)[C:38]2=[O:52])=[N:24][CH:25]=[CH:26][C:27]=1B1OC(C)(C)C(C)(C)O1)(=[O:19])[CH3:18].[O-]P([O-])([O-])=O.[K+].[K+].[K+].O.O.O.C([O-])(=O)C.[Na+]>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].O.C(#N)C>[C:17]([O:20][CH2:21][C:22]1[C:23]([N:37]2[N:46]=[CH:45][C:44]3[C:39](=[C:40]([F:51])[CH:41]=[C:42]([C:47]([CH3:49])([CH3:48])[CH3:50])[CH:43]=3)[C:38]2=[O:52])=[N:24][CH:25]=[CH:26][C:27]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[N:15][CH:14]=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:19])[CH3:18]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 23665404Sodium Acetate TrihydrateHCID 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 acetateHCID 866840855-Bromo-1-methyl-3-(pyrazin-2-ylamino)pyridin-2(1H)-one

Product 1

HCID 86684086(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-6-oxo-5-(pyrazin-2-ylamino)-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl AcetateYield 52.7%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 160a (140 mg, 0.50 mmol), 3-(acetoxymethyl)-2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)pyridin-4-ylboronic acid 116c (410 mg, 1.0 mmol), Pd(dppf)Cl2 (25 mg, 0.025 mmol), K3PO4 (220 mg, 1.0 mmol), sodium acetate trihydrate (136 mg, 1.0 mmol), acetonitrile (15 mL), and water (0.5 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 100° C. for 1 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (100:1 to 25:1) to afford 160b (150 mg, 52%) as a yellow solid. MS-ESI: [M+H]+ 570.2.

Workup

  1. customA 50-mL round-bottomed flask equipped with a reflux condenser
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. temperatureIt was then cooled to room temperature
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by silica-gel column chromatography
  8. washeluting with dichloromethane/methanol (100:1 to 25:1)

Sources & evidence

ORD record
ord-83a98d602ff14a6bb9f46a5c554b9b1e
Source dataset
uspto-grants-2014_03
Patent number
US08669251B2

Reaction notes

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