Sodium Carbonate → [5-(2-Fluoro-pyridin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

HRID 1921759Notes

Reaction equation

HRID 1921759 reaction equation
[F:1][C:2]1[CH:7]=[C:6](B(O)O)[CH:5]=[CH:4][N:3]=1.Br[C:12]1[N:17]2[CH:18]=[CH:19][N:20]=[C:16]2[C:15]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([N:28]3[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]3)=[CH:24][CH:23]=2)=[N:14][CH:13]=1.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>[NH3:3].[F:1][C:2]1[CH:7]=[C:6]([C:12]2[N:17]3[CH:18]=[CH:19][N:20]=[C:16]3[C:15]([NH:21][C:22]3[CH:23]=[CH:24][C:25]([N:28]4[CH2:29][CH2:30][N:31]([CH3:34])[CH2:32][CH2:33]4)=[CH:26][CH:27]=3)=[N:14][CH:13]=2)[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27833962-Fluoropyridine-4-boronic acidHCID 59022979(5-Bromoimidazo[1,2-a]pyrazin-8-yl)-(4-(4-methylpiperazin-1-yl)phenyl)amine

Product 2

HCID 222AmmoniaHCID 59023120[5-(2-Fluoro-pyridin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amineYield 61%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

In the same way as described for Compound 127, step 4, using 2-fluoro-pyridine-4-boronic acid (44 mg, 0.310 mmol), (5-bromo-imidazo[1,2-a]pyrazin-8-yl)-(4-(4-methylpiperazin-1-yl)phenyl)amine (60 mg, 0.155 mol), Pd(PPh3)4 (45 mg, 0.038 mmol) and 1.5M Na2CO3 (0.83 mL) in dioxane (2.2 mL). The residue is chromatographed on silica gel, eluting with DCM followed by 97:3 DCM:NH3 (7M in MeOH) affording the title compound (37.8 mg, 61%). LCMS: Rt 2.14 min (96%) m/z (APCI) 404 (M+H)+; 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 2.26 (3H, s), 2.49-2.54 (4H, t), 3.13-3.15 (4H, m), 6.97 (2H, d), 7.58 (1H, s), 7.71 (1H, s), 7.75 (2H, m), 7.89 (2H, d), 8.21 (1H, s), 8.43 (1H, d), 9.73 (1H, s).

Workup

  1. customThe residue is chromatographed on silica gel
  2. washeluting with DCM

Sources & evidence

ORD record
ord-33747286750444c3b276e0e21f9a84e7
Source dataset
uspto-grants-2012_05
Patent number
US08173656B2

Reaction notes

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