5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one → 5-(8-(4-(4-Isopropylpiperazin-1-yl)phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)isoindolin-1-one

HRID 605921Notes

Reaction equation

HRID 605921 reaction equation
[CH3:1][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:44]=N[C:46]([N:49]3[CH2:54][CH2:53][N:52]([CH:55]([CH3:57])[CH3:56])[CH2:51][CH2:50]3)=[CH:47][CH:48]=2)=[N:35][CH:34]=1.CC1(C)C(C)(C)OB([C:66]2[CH:67]=[C:68]3[C:72](=[CH:73][CH:74]=2)[C:71](=[O:75])[NH:70][CH2:69]3)O1>C([O-])([O-])=O.[Na+].[Na+].O1CCOCC1.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>[NH3:2].[CH:55]([N:52]1[CH2:51][CH2:50][N:49]([C:46]2[CH:1]=[CH:44][C:43]([NH:42][C:36]3[C:37]4[N:38]([N:39]=[CH:40][N:41]=4)[C:33]([C:66]4[CH:67]=[C:68]5[C:72](=[CH:73][CH:74]=4)[C:71](=[O:75])[NH:70][CH2:69]5)=[CH:34][N:35]=3)=[CH:48][CH:47]=2)[CH2:54][CH2:53]1)([CH3:56])[CH3:57]

Participants

8

Reactant 3

HCID 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 57590080(5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[6-(4-isopropylpiperazin-1-yl)pyridin-3-yl]amine

Product 2

HCID 222AmmoniaHCID 248891195-(8-(4-(4-Isopropylpiperazin-1-yl)phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)isoindolin-1-oneYield 53%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Procedure

This compound may be prepared using methods as described for Compound 6, step 4 using 5-bromo-N-(6-(4-isopropylpiperazin-1-yl)pyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine (0.6 g, 1.44 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-isoindol-1-one (0.56 g, 2.16 mmol) and Pd(PPh3)4 (0.416 g, 0.36 mmol) in 1.5M Na2CO3 (7.7 mL) and dioxane (23 mL). Purification by silica gel column chromatography eluting with DCM followed by 98:2 DCM:NH3 (7M in MeOH) affords the title compound (0.36 g, 53%) which is converted into the mesylate salt using 1M methanesulfonic acid in MeOH (0.77 mL). After trituration with diethyl ether and DCM the title compound is isolated as a solid (0.410 g). 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 1.35 (6H, d), 2.35 (3H, s, MsOH), 3.04 (2H, t), 3.20-3.27 (2H, m), 3.56-3.63 (3H, m), 3.89 (2H, d), 4.52 (2H, s), 7.09 (2H, d), 7.85 (1H, d), 7.95-8.01 (3H, m), 8.10 (1H, d), 8.24 (1H, s), 8.72 (1H, s), 8.74 (1H, s), 9.27 (1H, br s), 10.07 (1H, s). LCMS: Rt 2.93 min (97.9%), m/z (ES+) 469 (M+H)+.

Workup

  1. customThis compound may be prepared
  2. customPurification by silica gel column chromatography
  3. washeluting with DCM

Sources & evidence

ORD record
ord-364503f562f64d7b9f88b07568c02454
Source dataset
uspto-grants-2011_03
Patent number
US07915256B2

Reaction notes

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