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

HRID 1024095Notes

Reaction equation

HRID 1024095 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH:24]4[CH2:27][O:26][CH2:25]4)[CH2:20][CH2:19]3)=[CH:14][N:13]=2)[C:5]2[N:6]([N:8]=[CH:9][N:10]=2)[CH:7]=1.[C:28]([O:31][CH2:32][C:33]1[C:34]([N:48]2[CH2:60][CH2:59][N:51]3[C:52]4[CH2:53][CH2:54][CH2:55][CH2:56][C:57]=4[CH:58]=[C:50]3[C:49]2=[O:61])=[N:35][CH:36]=[CH:37][C:38]=1B1OC(C)(C)C(C)(C)O1)(=[O:30])[CH3:29].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[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>[C:28]([O:31][CH2:32][C:33]1[C:34]([N:48]2[CH2:60][CH2:59][N:51]3[C:52]4[CH2:53][CH2:54][CH2:55][CH2:56][C:57]=4[CH:58]=[C:50]3[C:49]2=[O:61])=[N:35][CH:36]=[CH:37][C:38]=1[C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:19][CH2:20][N:21]([CH:24]4[CH2:27][O:26][CH2:25]4)[CH2:22][CH2:23]3)=[CH:14][N:13]=2)[C:5]2[N:6]([N:8]=[CH:9][N:10]=2)[CH:7]=1)(=[O:30])[CH3:29]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866841346-Chloro-N-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)-[1,2,4]-triazolo[1,5-a]pyridin-8-amineHCID 86684143(2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate

Product 1

HCID 86684162(4-(8-(5-(4-(Oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl AcetateYield 56.9%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
140 °C

Procedure

A sealed tube was charged with 6-chloro-N-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)[1,2,4]triazolo[1,5-a]pyridin-8-amine 108d (196 mg, 0.51 mmol), 3-(acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic acid 114e (200 mg, 0.52 mmol), PdCl2(dppf) (24 mg, 0.030 mmol), K3PO4 (212 mg, 1.0 mmol), sodium acetate (83 mg, 1.0 mmol), acetonitrile (10 mL), and water (0.2 mL). The mixture was heated at 140° C. for 0.5 h. It was then cooled to room temperature and filtered. The filtrate was evaporated in vacuo. The residue was purified by silica-gel column chromatography eluting with 20:1 dichloromethane/methanol to afford 122a (200 mg, 56%) as a white solid. MS-ESI: [M+H]+ 689.3.

Workup

  1. temperatureIt was then cooled to room temperature
  2. filtrationfiltered
  3. customThe filtrate was evaporated in vacuo
  4. customThe residue was purified by silica-gel column chromatography
  5. washeluting with 20:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-e6d6420e29ce480f90d4e5dce6a89382
Source dataset
uspto-grants-2014_05
Patent number
US08722676B2

Reaction notes

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