Sodium Carbonate → 4-(8-(4-(2-Morpholinoethoxy)phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)thiophene-2-carboxamide

HRID 605909Notes

Reaction equation

HRID 605909 reaction equation
C[N:2]1CCN([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)CC1.BrC1N2N=CN=C2C(NC2C=CC([O:49][CH2:50][CH2:51][N:52]3[CH2:57][CH2:56][O:55][CH2:54][CH2:53]3)=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>[NH3:2].[O:55]1[CH2:56][CH2:57][N:52]([CH2:51][CH2:50][O:49][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)[CH2:53][CH2:54]1

Participants

8

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 575900074-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxamideHCID 57590052(5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-amine

Product 2

HCID 222AmmoniaHCID 248894674-(8-(4-(2-Morpholinoethoxy)phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)thiophene-2-carboxamideYield 52%

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-(2-morpholin-4-yl-ethoxy)-phenyl]-amine (113 mg, 0.27 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiophene-2-carboxamide (136 mg, 0.537 mmol), and Pd(PPh3)4 (78 mg, 0.067 mmol) in 1.5M Na2CO3 (1.44 mL, 2.16 mmol) and dioxane (4.3 mL). The reaction mixture is purified by silica gel column chromatography eluting with 97:3 DCM:NH3 (7M in MeOH) to yield the title compound (65 mg, 52%). LCMS: Rt 1.98 min (98.9%). Conversion into the mesylate salt using 0.1M methanesulfonic acid in MeOH (1.1385 mL) affords the title compound (50 mg, 95%). 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 2.37 (3H, s, MsOH), 3.21-3.64 (6H, m), 3.76 (2H, t), 4.05 (2H, d), 4.40 (2H, m), 7.09 (2H, d), 7.61 (1H, br s), 8.02 (2H, d), 8.11 (2H, s), 8.48 (1H, s), 8.67 (1H, s), 8.82 (1H, s), 9.91 (1H, br s), 10.09 (1H, s). LCMS: Rt 1.98 min (97.7%), m/z (APCI) 466 (M+H)+.

Workup

  1. customThis compound may be prepared
  2. customThe reaction mixture is purified by silica gel column chromatography
  3. washeluting with 97:3 DCM

Sources & evidence

ORD record
ord-ab2c9bada27e4046b8ead906121294bc
Source dataset
uspto-grants-2011_03
Patent number
US07915256B2

Reaction notes

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