Potassium Phosphate, Tribasic → (S)-4-Fluoro-2-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)benzyl acetate

HRID 519262Notes

Reaction equation

HRID 519262 reaction equation
[C:1]([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:24][CH2:23][C:22]3[N:21]4[C:16]([CH2:17][CH2:18][CH2:19][CH2:20]4)=[CH:15][C:14]=3[C:13]2=[O:25])=[CH:10][C:9]([F:26])=[CH:8][C:7]=1Br)(=[O:3])[CH3:2].[CH3:28][N:29]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[C:31]([NH:44][C:45]2[CH:50]=[CH:49][C:48]([N:51]3[CH2:56][CH2:55][N:54]([CH:57]4[CH2:60][O:59][CH2:58]4)[CH2:53][C@@H:52]3[CH3:61])=[CH:47][N:46]=2)[C:30]1=[O:62].CC(O[Na])=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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.CC#N>[C:1]([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:24][CH2:23][C:22]3[N:21]4[C:16]([CH2:17][CH2:18][CH2:19][CH2:20]4)=[CH:15][C:14]=3[C:13]2=[O:25])=[CH:10][C:9]([F:26])=[CH:8][C:7]=1[C:33]1[CH:32]=[C:31]([NH:44][C:45]2[CH:50]=[CH:49][C:48]([N:51]3[CH2:56][CH2:55][N:54]([CH:57]4[CH2:58][O:59][CH2:60]4)[CH2:53][C@@H:52]3[CH3:61])=[CH:47][N:46]=2)[C:30](=[O:62])[N:29]([CH3:28])[CH:34]=1)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 866837002-Bromo-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]-indolizin-2(1H)-yl)benzyl acetateHCID 866837011-methyl-3-((5-((2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-oneHCID 178418247HCID 178418247, compound

Product 1

HCID 86683699(S)-4-Fluoro-2-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)benzyl acetateYield 59%

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 mixture of 101h (300 mg, 0.70 mmol), (S)-1-methyl-3-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (332 mg, 0.70 mmol), CH3COONa (114 mg, 1.4 mmol), K3PO4 (368 mg, 1.4 mmol), PdCl2(dppf) (56 mg, 0.07 mmol), CH3CN (25 mL), and H2O (1 mL) was heated at 100° C. for 3 hours. It was then evaporated and the residue was purified by silical-gel column eluting with methylene chloride/methanol (30:1) to afford 101i (293 mg, yield 41%) as a brown solid. MS: (M+H)+ 710.

Workup

  1. customIt was then evaporated
  2. customthe residue was purified by silical-gel column
  3. washeluting with methylene chloride/methanol (30:1)

Sources & evidence

ORD record
ord-4bbe8db497cf414983fe952f17031676
Source dataset
uspto-grants-2015_08
Patent number
US09115152B2

Reaction notes

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