4-(1H-imidazol-1-yl)aniline → (5-Bromo-imidazo[1,2-a]pyrazin-8-yl)-(4-imidazol-1-yl-phenyl)-amine

HRID 1921790

Reaction equation

HRID 1921790 reaction equation
OC1C=CC(CNC(=O)C2C=CC(NC3C4N(C=CN=4)C(C4C=NNC=4)=CN=3)=CC=2)=CC=1.[Br:33][C:34]1[N:39]2[CH:40]=[CH:41][N:42]=[C:38]2[C:37](Br)=[N:36][CH:35]=1.[N:44]1([C:49]2[CH:54]=[CH:53][C:52]([NH2:55])=[CH:51][CH:50]=2)[CH:48]=[CH:47][N:46]=[CH:45]1.CC([O-])(C)C.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[Br:33][C:34]1[N:39]2[CH:40]=[CH:41][N:42]=[C:38]2[C:37]([NH:55][C:52]2[CH:51]=[CH:50][C:49]([N:44]3[CH:48]=[CH:47][N:46]=[CH:45]3)=[CH:54][CH:53]=2)=[N:36][CH:35]=1

Participants

8

Reactant 5

HCID 3201654-(1H-imidazol-1-yl)anilineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 24857547N-(4-Hydroxybenzyl)-4-[5-(1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-ylamino]benzamideHCID 534859495,8-Dibromoimidazo[1,2-a]pyrazine

Product 1

HCID 59023113(5-Bromo-imidazo[1,2-a]pyrazin-8-yl)-(4-imidazol-1-yl-phenyl)-amine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

In the same way as described for Compound 90, step 1, using 5,8-dibromoimidazo[1,2-a]pyrazine (203.8 mg, 0.736 mmol), 4-imidazol-1-yl-phenylamine (117.7 g, 0.739 mmol), NaOtBu (99 mg, 1.03 mmol), Pd2(dba)3 (27.0 mg, 0.0295 mmol), Xantphos (34.1 mg, 0.0589 mmol) and toluene (10 mL). The crude material is purified by Isolute FlashSilicaII cartridge chromatography eluting with 99:1 DCM:NH3 (7M in MeOH), followed by 97:3 DCM/NH3 (7M in MeOH). The title compound is isolated, after a second column chromatography purification using a 5:5:1 mixture EtOAc-petroleum ether-MeOH, as a yellow solid (104 mg, 40%).

Workup

  1. customThe crude material is purified by Isolute FlashSilicaII cartridge chromatography
  2. washeluting with 99:1 DCM

Sources & evidence

ORD record
ord-014a48bc794a434eaa6d96046db06f60
Source dataset
uspto-grants-2012_05
Patent number
US08173656B2

Linked notes

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