Sodium Carbonate → 5-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}-thiophene-2-carboxylic acid amide

HRID 605902Notes

Reaction equation

HRID 605902 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]3[C:16]4[N:17]([N:29]=[CH:30][N:31]=4)[C:18](C4C=C(C(N)=O)SC=4)=[CH:19][N:20]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.CN1CCN(C2C=CC(N)=CC=2)CC1.CC1(C)C(C)(C)OB([C:54]2[S:58][C:57]([C:59]([NH2:61])=[O:60])=[CH:56][CH:55]=2)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].[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]([NH:14][C:15]3[C:16]4[N:17]([N:29]=[CH:30][N:31]=4)[C:18]([C:54]4[S:58][C:57]([C:59]([NH2:61])=[O:60])=[CH:56][CH:55]=4)=[CH:19][N:20]=3)=[CH:12][CH:13]=2)[CH2:4][CH2:3]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 7372534-(4-Methylpiperazin-1-yl)anilineHCID 575899284-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}-thiophene-2-carboxylic acid amideHCID 575899405-(Tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxamide

Product 2

HCID 222AmmoniaHCID 575900115-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}-thiophene-2-carboxylic acid amideYield 21%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

This compound may be prepared using methods as described for Compound 6, step 4 using 5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (100 mg, 0.258 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxa-borolan-2-yl)-thiophene-2-carboxylic acid amide (130 mg, 0.516 mmol) and Pd(PPh3)4 (74 mg, 0.0645 mmol) in aqueous 1.5M Na2CO3 (1.37 mL, 2.06 mmol) and dioxane (2.75 mL). After evaporation of the solvent, the residue is purified by silica gel column chromatography eluting with 96:6 DCM:NH3 (7M in MeOH) to afford the title compound (23 mg, 21%). LCMS: Rt 1.94 min (97.9%). 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 2.26 (3H, s), 2.49 (4H, m), 3.14 (4H, m), 6.98 (2H, d), 7.51 (1H, br s), 7.85-7.89 (2H, m), 8.03 (2H, d), 8.10 (1H, br s), 8.38 (1H, s), 8.82 (1H, s), 10.10 (1H, s). LCMS: Rt 1.94 min, (97.9%), m/z (APCI) 435 (M+H)+.

Workup

  1. customThis compound may be prepared
  2. customAfter evaporation of the solvent
  3. customthe residue is purified by silica gel column chromatography
  4. washeluting with 96:6 DCM

Sources & evidence

ORD record
ord-6e553980a417495c9a52989bf26bcfb4
Source dataset
uspto-grants-2011_03
Patent number
US07915256B2

Reaction notes

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