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

HRID 605904Notes

Reaction equation

HRID 605904 reaction equation
CN1[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]([C:21]4[CH:22]=[C:23]([C:26]([NH2:28])=[O:27])[S:24][CH:25]=4)=[CH:19][N:20]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.BrC1N2N=CN=C2C(NC2C=CC(N3CC[O:52]CC3)=CC=2)=NC=1.CC1(C)C(C)(C)OB(C2C=C(C(N)=O)SC=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>[N:5]1([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:21]4[CH:22]=[C:23]([C:26]([NH2:28])=[O:27])[S:24][CH:25]=4)=[CH:19][N:20]=3)=[CH:12][CH:13]=2)[CH2:6][CH2:7][O:52][CH2:3][CH2:4]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 575899284-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}-thiophene-2-carboxylic acid amideHCID 57589931(5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-(4-morpholin-4-ylphenyl)amineHCID 575900074-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxamide

Product 1

HCID 248896314-[8-(4-Morpholin-4-yl-phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]-thiophene-2-carboxylic acid amideYield 37.4%

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-morpholin-4-yl-phenyl)-amine (0.2 g, 0.53 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiophene-2-carboxylic acid amide (0.27 mg, 1.06 mmol), and Pd(PPh3)4 (0.15 mg, 0.133 mmol) in 1.5M Na2CO3 (aq) (2.84 mL, 4.26 mmol) and dioxane (10 mL). The reaction mixture is partitioned between water and ethyl acetate. A precipitate is formed, collected by filtration and purified by silica gel column chromatography using 95:5 DCM:MeOH to give the title compound (84.1 mg, 37.4%). 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 3.13 (4H, m), 3.79 (4H, m), 7.01 (2H, d), 7.60 (1H, br s), 7.91 (2H, d), 8.10 (2H, s), 8.48 (1H, s), 8.66 (1H, s), 8.79 (1H, s), 9.96 (1H, s). LCMS: Rt 2.61 min (97.1%), m/z (APCI) 422 (M+H)+.

Workup

  1. customThis compound may be prepared
  2. customThe reaction mixture is partitioned between water and ethyl acetate
  3. customA precipitate is formed
  4. filtrationcollected by filtration
  5. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-9d76bee2c3a044cc96f7cbde65732fed
Source dataset
uspto-grants-2011_03
Patent number
US07915256B2

Reaction notes

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