Water → 2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

HRID 407615Notes

Reaction equation

HRID 407615 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[N:24]=[CH:23][CH:22]=[C:21](Cl)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[CH3:26][N:27]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[C:29]([NH:42][C:43]2[CH:48]=[CH:47][C:46]([N:49]3[CH2:54][CH2:53][N:52]([CH:55]4[CH2:58][O:57][CH2:56]4)[CH2:51][CH2:50]3)=[CH:45][N:44]=2)[C:28]1=[O:59].O>C1COCC1.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:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[N:24]=[CH:23][CH:22]=[C:21]([C:31]3[CH:30]=[C:29]([NH:42][C:43]4[CH:48]=[CH:47][C:46]([N:49]5[CH2:54][CH2:53][N:52]([CH:55]6[CH2:56][O:57][CH2:58]6)[CH2:51][CH2:50]5)=[CH:45][N:44]=4)[C:28](=[O:59])[N:27]([CH3:26])[CH:32]=3)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 962WaterHCID 866839131-methyl-3-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2(1H)-oneHCID 866839152-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde

Product 1

HCID 866839162-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehydeYield 80.6%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 103b (100 mg, 0.28 mmol), 1-methyl-3-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridine-2-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (131 mg, 0.28 mmol), PdCl2(dppf) (25 mg, 0.03 mmol), and K3PO4.3H2O (149 mg, 0.56 mmol) was suspended in THF (10 mL)/H2O (5 mL). After three cycles of vacuum/argon flash, the mixture was heated at 70° C. for 6 h. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified on flash column chromatography eluting with 1:3 petroleum/ethyl acetate to afford 103c as a yellow solid (150 mg, 60%). LCMS: [M+H]+ 665

Workup

  1. filtrationIt was then filtered
  2. customthe filtrate was evaporated in vacuo
  3. customThe residue was purified on flash column chromatography
  4. washeluting with 1:3 petroleum/ethyl acetate

Sources & evidence

ORD record
ord-1b1398ad8e294ff99bb5afa143a40638
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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