(5-Bromoimidazo[1,2-a]pyrazin-8-yl)-(4-(4-methylpiperazin-1-yl)phenyl)amine → 2-Fluoro-4-{8-[4-(4-methylpiperazin-1-yl)phenylamino]imidazo[1,2-a]pyrazin-5-yl}benzamide

HRID 1921758Notes

Reaction equation

HRID 1921758 reaction equation
[F:1][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>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].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>[F:1][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:32]=[CH:33][C:34]([N:37]4[CH2:38][CH2:39][N:40]([CH3:43])[CH2:41][CH2:42]4)=[CH:35][CH:36]=3)=[N:23][CH:22]=2)[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5]

Participants

6

Reactant 2

HCID 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 590230422-Fluoro-4-{8-[4-(4-methylpiperazin-1-yl)phenylamino]imidazo[1,2-a]pyrazin-5-yl}benzamide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 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 (82 mg, 0.31 mmol), (5-bromoimidazo[1,2-a]pyrazin-8-yl)-(4-(4-methylpiperazin-1-yl)phenyl)amine (60 mg, 0.155 mmol) and Pd(PPh3)4 (45 mg, 0.038 mmol) in dioxane (2.2 mL) and 1.5M Na2CO3 (0.83 mL). The residue is chromatographed on silica gel, eluting with DCM followed by 96:4 DCM:NH3 (7M in MeOH), and the fractions containing the desired product are combined and evaporated. The residue is triturated with Et2O to afford the title compound as a solid. HPLC (254 nm): Rt 1.94 min (93.5%); m/z (APCI) 446 (M+H)+

Workup

  1. customThe residue is chromatographed on silica gel
  2. washeluting with DCM
  3. additionNH3 (7M in MeOH), and the fractions containing the desired product
  4. customevaporated
  5. customThe residue is triturated with Et2O

Sources & evidence

ORD record
ord-44baed002ebf4837b21f6392a775f417
Source dataset
uspto-grants-2012_05
Patent number
US08173656B2

Reaction notes

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