Potassium Phosphate, Tribasic → 4-Fluoro-2-(8-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate

HRID 1024037Notes

Reaction equation

HRID 1024037 reaction equation
[C:1]([O:4][CH2:5][C:6]1[C:11](B2OC(C)(C)C(C)(C)O2)=[CH:10][C:9]([F:21])=[CH:8][C:7]=1[N:22]1[CH2:34][CH2:33][N:25]2[C:26]3[CH2:27][CH2:28][CH2:29][CH2:30][C:31]=3[CH:32]=[C:24]2[C:23]1=[O:35])(=[O:3])[CH3:2].Cl[C:37]1[CH:38]=[C:39]([NH:46][C:47]2[CH:52]=[CH:51][C:50]([N:53]3[CH2:58][CH2:57][N:56]([CH:59]4[CH2:62][O:61][CH2:60]4)[CH2:55][CH2:54]3)=[CH:49][N:48]=2)[C:40]2[N:41]([N:43]=[CH:44][N:45]=2)[CH:42]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC([O-])=O.[Na+]>CC#N.O.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]([O:4][CH2:5][C:6]1[C:7]([N:22]2[CH2:34][CH2:33][N:25]3[C:26]4[CH2:27][CH2:28][CH2:29][CH2:30][C:31]=4[CH:32]=[C:24]3[C:23]2=[O:35])=[CH:8][C:9]([F:21])=[CH:10][C:11]=1[C:37]1[CH:38]=[C:39]([NH:46][C:47]2[CH:52]=[CH:51][C:50]([N:53]3[CH2:58][CH2:57][N:56]([CH:59]4[CH2:60][O:61][CH2:62]4)[CH2:55][CH2:54]3)=[CH:49][N:48]=2)[C:40]2[N:41]([N:43]=[CH:44][N:45]=2)[CH:42]=1)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 580442052-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl AcetateHCID 866841346-Chloro-N-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)-[1,2,4]-triazolo[1,5-a]pyridin-8-amine

Product 1

HCID 866841364-Fluoro-2-(8-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetateYield 93.2%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
110 °C

Procedure

A mixture of 4-fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate 101l (165 mg, 0.38 mmol), 108d (140 mg, 0.38 mmol), PdCl2(dppf) (41 mg, 0.056 mmol), K3PO4 (100 mg), and NaOAc (50 mg) in MeCN (10 mL) and H2O (3 mL) was heated at 110° C. in sealed tube for 2 h. The solvent was evaporated in vacuo and the residue was purified by silica gel chromatography to afford 108e (250 mg, 60%). MS: [M+H]+ 706.

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-6cb689d7ec7346fa9dfa95c0bb908ace
Source dataset
uspto-grants-2014_05
Patent number
US08722676B2

Reaction notes

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