Sodium Carbonate → 5-(8-(4-(4-Isopropyl-2-oxopiperazin-1-yl)phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)isoindolin-1-one

HRID 605981Notes

Reaction equation

HRID 605981 reaction equation
C[N:2]1CCN(C2C=CC(NC3C4N(N=CN=4)C(C4C=C(C(N)=O)SC=4)=CN=3)=CC=2)CC1.Br[C:33]1[N:38]2[N:39]=[CH:40][N:41]=[C:37]2[C:36]([NH:42][C:43]2[CH:48]=[CH:47][C:46]([N:49]3[CH2:54][CH2:53][N:52]([CH:55]([CH3:57])[CH3:56])[CH2:51][C:50]3=[O:58])=[CH:45][CH:44]=2)=[N:35][CH:34]=1.CC1(C)C(C)(C)OB([C:67]2[CH:68]=[C:69]3[C:73](=[CH:74][CH:75]=2)[C:72](=[O:76])[NH:71][CH2:70]3)O1.C([O-])([O-])=O.[Na+].[Na+]>[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1.O1CCOCC1>[NH3:2].[CH:55]([N:52]1[CH2:53][CH2:54][N:49]([C:46]2[CH:47]=[CH:48][C:43]([NH:42][C:36]3[C:37]4[N:38]([N:39]=[CH:40][N:41]=4)[C:33]([C:67]4[CH:68]=[C:69]5[C:73](=[CH:74][CH:75]=4)[C:72](=[O:76])[NH:71][CH2:70]5)=[CH:34][N:35]=3)=[CH:44][CH:45]=2)[C:50](=[O:58])[CH2:51]1)([CH3:57])[CH3:56]

Participants

10

Reactant 4

HCID 10340Sodium CarbonateHCID 219557955-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 575899284-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}-thiophene-2-carboxylic acid amideHCID 575900031-[4-(5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino)-phenyl]-4-isopropyl-piperazin-2-one

Product 2

HCID 222AmmoniaHCID 248896275-(8-(4-(4-Isopropyl-2-oxopiperazin-1-yl)phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)isoindolin-1-oneYield 55%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

This compound may be prepared using methods as described for Compound 6, step 4, using 1-[4-(5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino)-phenyl]-4-isopropyl-piperazin-2-one (40 mg, 0.09 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-isoindol-1-one (37 mg, 0.14 mmol), and Pd(PPh3)4 (31 mg, 0.027 mmol) in 1.5M Na2CO3 (aq) (0.5 mL, 0.75 mmol), and dioxane (1.2 mL). The reaction mixture is diluted with brine then toluene is added and a precipitate is formed and collected by filtration. The filtrate is washed with diethyl ether, petroleum ether and MeOH and then purified by silica gel column chromatography. Elution with 99:1 DCM:NH3 (7M in MeOH) followed by 98:2 and 95:5 DCM:NH3 (7M in MeOH) affords the title compound as a yellow solid (24 mg, 55%). 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 1.08 (6H, d), 2.73-2.87 (3H, m), 3.27 (2H, s), 3.62-3.68 (2H, m), 4.52 (2H, s), 7.36 (2H, d), 7.84 (1H, d), 8.07-8.10 (4H, m), 8.25 (1H, s), 8.70 (1H, br s), 8.77 (1H, s), 10.28 (1H, s). LCMS: Rt 1.94 min (95.2%), m/z (APCI) 483 (M+H)+.

Workup

  1. customThis compound may be prepared
  2. customa precipitate is formed
  3. filtrationcollected by filtration
  4. washThe filtrate is washed with diethyl ether, petroleum ether and MeOH
  5. custompurified by silica gel column chromatography
  6. washElution with 99:1 DCM

Sources & evidence

ORD record
ord-a9b153ee739d4365b0fa5d3133f55638
Source dataset
uspto-grants-2011_03
Patent number
US07915256B2

Reaction notes

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