Potassium Phosphate, Tribasic → 2-(10-Fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(1-methyl-6-oxo-5-(pyrimidin-4-ylamino)-1,6-dihydropyridin-3-yl)nicotinaldehyde

HRID 1411609Notes

Reaction equation

HRID 1411609 reaction equation
Cl[C:2]1[C:7]([CH:8]=[O:9])=[C:6]([N:10]2[CH2:23][CH2:22][N:13]3[C:14]4[CH2:15][CH2:16][CH2:17][CH2:18][C:19]=4[C:20]([F:21])=[C:12]3[C:11]2=[O:24])[N:5]=[CH:4][CH:3]=1.[CH3:25][N:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[C:28]([NH:41][C:42]2[CH:47]=[CH:46][N:45]=[CH:44][N:43]=2)[C:27]1=[O:48].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC([O-])=O.[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>[F:21][C:20]1[C:19]2[CH2:18][CH2:17][CH2:16][CH2:15][C:14]=2[N:13]2[CH2:22][CH2:23][N:10]([C:6]3[N:5]=[CH:4][CH:3]=[C:2]([C:30]4[CH:29]=[C:28]([NH:41][C:42]5[CH:47]=[CH:46][N:45]=[CH:44][N:43]=5)[C:27](=[O:48])[N:26]([CH3:25])[CH:31]=4)[C:7]=3[CH:8]=[O:9])[C:11](=[O:24])[C:12]=12

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 580438621-methyl-3-(pyrimidin-4-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 866842384-Chloro-2-(10-fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehyde

Product 1

HCID 866842572-(10-Fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(1-methyl-6-oxo-5-(pyrimidin-4-ylamino)-1,6-dihydropyridin-3-yl)nicotinaldehydeYield 27%

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 round-bottomed flask was charged with 146a (200 mg, 0.58 mmol), 1-methyl-3-(pyrimidin-4-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one 143a (227 mg, 0.69 mmol), PdCl2(dppf) (47 mg, 0.06 mmol), K3PO4 (244 mg, 1.15 mmol), NaOAc (94 mg, 1.15 mmol), acetonitrile (30 mL), and H2O (3 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 3 h. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified on flash column chromatography eluting with 1:20 methanol/dichloro-methane to afford 146b as a red solid (79 mg, 27%). LCMS: [M+H]+ 514

Workup

  1. customAfter three cycles of vacuum/argon flush
  2. filtrationIt was then filtered
  3. customthe filtrate was evaporated in vacuo
  4. customThe residue was purified on flash column chromatography
  5. washeluting with 1:20 methanol/dichloro-methane

Sources & evidence

ORD record
ord-1450e06cbe7e45a5a60a8585a52869dc
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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