Methyl 4-aminobenzoate → 4-(5-Bromoimidazo[1,2-a]pyrazin-8-ylamino)benzoic acid methyl ester

HRID 1921741Notes

Reaction equation

HRID 1921741 reaction equation
[Br:1][C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[C:5](Br)=[N:4][CH:3]=1.[CH3:12][O:13][C:14](=[O:22])[C:15]1[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=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>[CH3:12][O:13][C:14](=[O:22])[C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:5]2[C:6]3[N:7]([CH:8]=[CH:9][N:10]=3)[C:2]([Br:1])=[CH:3][N:4]=2)=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 12082Methyl 4-aminobenzoateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 534859495,8-Dibromoimidazo[1,2-a]pyrazine

Product 1

HCID 590230964-(5-Bromoimidazo[1,2-a]pyrazin-8-ylamino)benzoic acid methyl ester

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 5,8-dibromoimidazo[1,2-a]pyrazine (2 g, 7.3 mmol), 4-amino benzoic acid methyl ester (0.93 g, 6.2 mmol), NaOtBu (0.98 g, 10.2 mmol), Pd2(dba)3 (133 mg, 0.14 mmol), Xantphos (168 mg, 0.29 mmol) and toluene is degassed with nitrogen, then heated at 85° C. for 18 hours. The toluene is removed in vacuo, then MeOH is added to the crude residue. The solid is collected by filtration and dried in the vacuum oven. The solid is identified as the desired title ester. The filtrate is chromatographed with petrol:EtOAc (70:30 followed by 50:50) and the fractions containing the desired product, combined, evaporated and triturated with MeOH. The resultant solid is collected by filtration and is also identified as the desired ester.

Workup

  1. customis degassed with nitrogen
  2. customThe toluene is removed in vacuo
  3. additionMeOH is added to the crude residue
  4. filtrationThe solid is collected by filtration
  5. customdried in the vacuum oven
  6. customThe filtrate is chromatographed with petrol:EtOAc (70:30 followed by 50:50)
  7. additionthe fractions containing the desired product
  8. customevaporated
  9. customtriturated with MeOH
  10. filtrationThe resultant solid is collected by filtration

Sources & evidence

ORD record
ord-ccc080047cf94028a7e9f8e02cff80b8
Source dataset
uspto-grants-2012_05
Patent number
US08173656B2

Reaction notes

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