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

HRID 605913

Reaction equation

HRID 605913 reaction equation
C[N:2]1CCN(C2C=CC(NC3C4N(N=CN=4)C([C:21]4[CH:22]=[C:23]([C:26]([NH2:28])=[O:27])[S:24][CH:25]=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.[CH3:58]C1(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].[CH:55]([N:52]1[CH2:51][CH2:50][N:49]([C:46]2[CH:58]=[CH:44][C:43]([NH:42][C:36]3[C:37]4[N:38]([N:39]=[CH:40][N:41]=4)[C:33]([C:21]4[CH:22]=[C:23]([C:26]([NH2:28])=[O:27])[S:24][CH:25]=4)=[CH:34][N:35]=3)=[CH:48][CH:47]=2)[CH2:54][CH2:53]1)([CH3:56])[CH3:57]

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 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 248892914-(8-(4-(4-Isopropylpiperazin-1-yl)phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)thiophene-2-carboxamideYield 61%

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-N-(6-(4-isopropylpiperazin-1-yl)pyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine (100 mg, 0.24 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiophene-2-carboxamide (121 mg, 0.48 mmol), and Pd(PPh3)4 (69 mg, 0.059 mmol) in 1.5M Na2CO3 (1.28 mL, 1.92 mmol) and dioxane (3.84 mL). The crude product is purified by silica gel column chromatography eluting with DCM and 97:3 DCM:NH3 (7M in MeOH) to yield the title compound (68 mg, 61%) as a pale green solid. Conversion into the mesylate salt using 0.1M methanesulfonic acid in MeOH (1.47 mL, 0.147 mmol) followed by trituration with DCM and diethyl ether, affords the title compound (67 mg, 98.5%). 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 1.35 (6H, d), 2.34 (3H, s, MsOH), 3.00 (2H, t), 3.22-3.25 (2H, m), 3.56-3.61 (3H, m), 3.89 (2H, d), 7.09 (2H, d), 7.60 (1H, br s), 7.97 (2H, d), 8.10 (2H, s), 8.48 (1H, s), 8.67 (1H, s), 8.81 (1H, s), 9.23 (1H, br s), 10.03 (1H, s). LCMS: Rt 2.13 min (98.4%), m/z (APCI) 463 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-f37448386f6744bdbd8a9acfcce11669
Source dataset
uspto-grants-2011_03
Patent number
US07915256B2

Linked notes

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