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

HRID 407622Notes

Reaction equation

HRID 407622 reaction equation
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH2:29][CH2:28][N:27]([CH:30]4[CH2:33][O:32][CH2:31]4)[CH2:26][C@H:25]3[CH3:34])=[CH:20][N:19]=2)[C:3]1=[O:35].[C:36]([C:40]1[CH:41]=[C:42]2[C:47](=[C:48]([F:50])[CH:49]=1)[C:46](=[O:51])[N:45]([C:52]1[N:59]=[CH:58][CH:57]=[C:56](Cl)[C:53]=1[CH:54]=[O:55])[N:44]=[CH:43]2)([CH3:39])([CH3:38])[CH3:37].CC([O-])=O.[Na+].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(#N)C.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:36]([C:40]1[CH:41]=[C:42]2[C:47](=[C:48]([F:50])[CH:49]=1)[C:46](=[O:51])[N:45]([C:52]1[N:59]=[CH:58][CH:57]=[C:56]([C:6]3[CH:5]=[C:4]([NH:17][C:18]4[CH:23]=[CH:22][C:21]([N:24]5[CH2:29][CH2:28][N:27]([CH:30]6[CH2:33][O:32][CH2:31]6)[CH2:26][C@H:25]5[CH3:34])=[CH:20][N:19]=4)[C:3](=[O:35])[N:2]([CH3:1])[CH:7]=3)[C:53]=1[CH:54]=[O:55])[N:44]=[CH:43]2)([CH3:39])([CH3:37])[CH3:38]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866839152-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehydeHCID 866839191-methyl-3-[[5-[(2R)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one

Product 1

HCID 86683920(R)-2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazine-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehydeYield 34%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of 106a (260.0 mg, 0.56 mmol), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde 103b (200.0 mg, 0.56 mmol), PdCl2(dppf) (50.0 mg, 0.056 mmol), NaOAc (90.0 mg, 1.1 mmol), K3PO4 (300 mg, 1.1 mmol) in acetonitrile (30 mL) was heated at 100° C. for 3 h. The solvent was evaporated in vacuo. The residue was purified by flash column chromatography eluting with CH2Cl2/methanol (10:1) to afford 106b (120 mg, 34%) as a brown solid. LCMS: [M+H]+ 679.3

Workup

  1. customThe solvent was evaporated in vacuo
  2. customThe residue was purified by flash column chromatography
  3. washeluting with CH2Cl2/methanol (10:1)

Sources & evidence

ORD record
ord-c8620461df4243bdba6510d8ee69b773
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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