Dimethylformamide → 2-Dimethylamino-4-{8-[4-(4-methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-benzamide

HRID 1366136Notes

Reaction equation

HRID 1366136 reaction equation
F[C:2]1[CH:10]=[C:9](B2OC(C)(C)C(C)(C)O2)[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].Br[C:21]1[N:26]2[CH:27]=[CH:28][N:29]=[C:25]2[C:24]([NH:30][C:31]2[CH:36]=[CH:35][C:34]([N:37]3[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][CH2:38]3)=[CH:33][CH:32]=2)=[N:23][CH:22]=1.C([O-])([O-])=O.[Na+].[Na+].[CH3:50][N:51](C)[CH:52]=O>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>[CH3:50][N:51]([CH3:52])[C:2]1[CH:10]=[C:9]([C:21]2[N:26]3[CH:27]=[CH:28][N:29]=[C:25]3[C:24]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([N:37]4[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][CH2:38]4)=[CH:33][CH:32]=3)=[N:23][CH:22]=2)[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 59022979(5-Bromoimidazo[1,2-a]pyrazin-8-yl)-(4-(4-methylpiperazin-1-yl)phenyl)amineHCID 590230642-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide

Product 1

HCID 590229862-Dimethylamino-4-{8-[4-(4-methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-benzamide

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-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (148 mg, 0.414 mmol), (5-bromoimidazo[1,2-a]pyrazin-8-yl)-(4-(4-methylpiperazin-1-yl)phenyl)amine (80 mg, 0.279 mol) and Pd(PPh3)4 (81 mg, 0.069 mmol) and 1.5M Na2CO3 (1.49 mL), in dioxane (0.93 mL) and N,N-dimethylformamide (2.06 mL). The residue is chromatographed on silica gel, eluting with DCM followed by 96:4 DCM:NH3 (7M in MeOH). The compound, isolated after additional purification by reverse phase prep HPLC is 2-dimethylamino-4-{8-[4-(4-methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-benzamide (3.2 mg). LCMS: Rt 1.67 min (97%) m/z (APCI) 471 (M+H)+; 1H-NMR (400 MHz, d6-DMSO) δ (ppm).2.26 (3H, s), 2.48-2.53 (4H, m), 2.85 (6H, s), 3.12-3.14 (4H, m), 6.96 (2H, d), 7.32 (1H, d), 7.36 (1H, d), 7.52 (1H, s), 7.54 (1H, br s), 7.71 (1H, s), 7.74 (1H, d), 7.91 (2H, d), 8.02 (1H, s), 8.28 (1H, br s), 9.48 (1H, s).

Workup

  1. customThe residue is chromatographed on silica gel
  2. washeluting with DCM
  3. customThe compound, isolated
  4. customafter additional purification by reverse phase prep HPLC

Sources & evidence

ORD record
ord-f837c85a14664bb0a84e4aec02eb7188
Source dataset
uspto-grants-2011_02
Patent number
US07893058B2

Reaction notes

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