4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → 5-(5-(1H-Pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino)-2-morpholinobenzamide

HRID 605908

Reaction equation

HRID 605908 reaction equation
C[N:2]1CCN(C2C=CC(NC3C4[N:17]([N:29]=[CH:30]N=4)[C:18]([C:21]4C=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]=[CH:45][C:46]([N:52]3[CH2:57][CH2:56][O:55][CH2:54][CH2:53]3)=[C:47]([CH:51]=2)[C:48]([NH2:50])=[O:49])=[N:35][CH:34]=1.CC1(C)C(C)(C)OB(C2C=NNC=2)O1>C([O-])([O-])=O.[K+].[K+].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].[NH:17]1[CH:18]=[C:21]([C:33]2[N:38]3[N:39]=[CH:40][N:41]=[C:37]3[C:36]([NH:42][C:43]3[CH:44]=[CH:45][C:46]([N:52]4[CH2:53][CH2:54][O:55][CH2:56][CH2:57]4)=[C:47]([CH:51]=3)[C:48]([NH2:50])=[O:49])=[N:35][CH:34]=2)[CH:30]=[N:29]1

Participants

8

Reactant 3

HCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 575899284-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}-thiophene-2-carboxylic acid amideHCID 575900535-(5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino)-2-morpholin-4-yl-benzamide

Product 2

HCID 222AmmoniaHCID 1359796085-(5-(1H-Pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino)-2-morpholinobenzamideYield 30%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 11430Potassium CarbonateSolventHCID 312751,4-DioxaneSolvent

Procedure

This compound may be prepared using methods as described for Compound 6, step 4 using 5-(5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino)-2-morpholin-4-yl-benzamide (140 mg, 0.33 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (130 mg, 0.67 mmol) and Pd(PPh3)4 (96 mg, 0.083 mmol) in 1.5M K2CO3 (aq) (1.93 mL) and dioxane (3.44 mL). The crude material is purified by silica gel column chromatography eluting with DCM followed by 99:1 then 97:3 then 95:5 DCM:NH3 (7M in MeOH) to afford the title compound as a white solid (40.5 mg, 30%). 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 2.96 (4H, m), 3.79 (4H, m), 7.28 (2H, d), 7.45 (1H, m), 7.54 (1H, br s), 8.01-8.09 (1H, dd), 8.25 (1H, s), 8.50 (1H, d), 8.69 (1H, br s), 8.78 (1H, s), 9.98 (1H, s), 13.3 (1H, br s). LCMS: Rt 2.23 min (96.9%), m/z (APCI) 406 (M+H)+.

Workup

  1. customThis compound may be prepared
  2. customThe crude material is purified by silica gel column chromatography
  3. washeluting with DCM

Sources & evidence

ORD record
ord-5b177b5c589646038abde62b94596b4e
Source dataset
uspto-grants-2011_03
Patent number
US07915256B2

Linked notes

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