Water → 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(6-(5-(morpholine-4-carbonyl)pyridin-2-ylamino)pyrimidin-4-yl)benzyl acetate

HRID 402956Notes

Reaction equation

HRID 402956 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][C:12]([C:15]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[O:16])=[CH:11][CH:10]=2)[CH:3]=1.[C:23]([O:26][CH2:27][C:28]1[C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][CH:31]=[CH:30][C:29]=1[N:43]1[N:52]=[CH:51][C:50]2[C:45](=[C:46]([F:57])[CH:47]=[C:48]([C:53]([CH3:56])([CH3:55])[CH3:54])[CH:49]=2)[C:44]1=[O:58])(=[O:25])[CH3:24].C([O-])([O-])=O.[Na+].[Na+].O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:53]([C:48]1[CH:49]=[C:50]2[C:45](=[C:46]([F:57])[CH:47]=1)[C:44](=[O:58])[N:43]([C:29]1[CH:30]=[CH:31][CH:32]=[C:33]([C:2]3[CH:3]=[C:4]([NH:8][C:9]4[CH:10]=[CH:11][C:12]([C:15]([N:17]5[CH2:22][CH2:21][O:20][CH2:19][CH2:18]5)=[O:16])=[CH:13][N:14]=4)[N:5]=[CH:6][N:7]=3)[C:28]=1[CH2:27][O:26][C:23](=[O:25])[CH3:24])[N:52]=[CH:51]2)([CH3:54])([CH3:55])[CH3:56]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 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 86686852HCID 86686852, compound

Product 1

HCID 866868532-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(6-(5-(morpholine-4-carbonyl)pyridin-2-ylamino)pyrimidin-4-yl)benzyl acetateYield 30.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of (6-(6-chloropyrimidin-4-ylamino)pyridin-3-yl)(morpholino)methanone (0.15 g, 0.45 mmol) in 1,4-dioxane (5 mL) was added 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 (0.250 g, 0.5 mmol), Pd(PPh3)4 (30 mg, 0.08 mmol), Na2CO3(212 mg, 2 mmol) and H2O (2 mL). The mixture was stirred at 80° C. for 13 hrs under N2. The mixture was evaporated and ethyl acetate (50 mL) and H2O (20 mL) were added to the resulting residue. The organic phase was washed with H2O (2×20 mL), brine (2×20 mL) and dried over Na2SO4. After filtration and concentration, the final product (90 mg, 30%) was obtained as yellow solid. LC-MS: 652.2 [M+H]+, tR=1.499 min.

Workup

  1. customThe mixture was evaporated
  2. additionethyl acetate (50 mL) and H2O (20 mL) were added to the resulting residue
  3. washThe organic phase was washed with H2O (2×20 mL), brine (2×20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationAfter filtration and concentration

Sources & evidence

ORD record
ord-88daa36b95fb47ba98704e1bf861e511
Source dataset
uspto-grants-2014_06
Patent number
US08742098B2

Reaction notes

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