Sodium Carbonate → tert-butyl 4-[6'-amino-5'-(6-methoxy-1 H-benzimidazol-2-yl)-[3,3']bipyridinyl-6-yl]piperazine-1-carboxylate

HRID 241410Notes

Reaction equation

HRID 241410 reaction equation
I[C:2]1[CH:3]=[C:4]([C:9]2[NH:13][C:12]3[CH:14]=[CH:15][C:16]([O:18][CH3:19])=[CH:17][C:11]=3[N:10]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[CH:30][C:31]([N:34]3[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]3)=[N:32][CH:33]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.O.C(OCC)(=O)C.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>[NH2:8][C:5]1[N:6]=[CH:7][C:2]([C:28]2[CH:33]=[N:32][C:31]([N:34]3[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]3)=[CH:30][CH:29]=2)=[CH:3][C:4]=1[C:9]1[NH:10][C:11]2[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:12]=2[N:13]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 16217947Tert-butyl 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine-1-carboxylateHCID 178488052HCID 178488052, compound

Product 1

HCID 67494746tert-butyl 4-[6'-amino-5'-(6-methoxy-1 H-benzimidazol-2-yl)-[3,3']bipyridinyl-6-yl]piperazine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 22728543Water ethylacetateSolvent

Procedure

128.87 mg (0.273 mmol) of 5-iodo-3-(5-methoxy-1H-benzimidazol-2-yl)pyridin-2-ylamine and 191.38 mg (0.492 mmol) of tert-butyl 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]piperazine-1-carboxylate are suspended in 2.5 ml of N,N-dimethylformamide in a nitrogen-filled microwave vessel, and 0.6 ml (1.2 mmol) of 2M sodium carbonate solution and 31.5 mg (0.027 mmol) of tetrakis(triphenylphosphine)palladium(0) are added. The reaction solution is irradiated with microwaves for 30 min at 120° C. in the Biotage SmithSynthesizer. The reaction mixture is cooled to room temperature and diluted with water/ethyl acetate and filtered. The aqueous phase is extracted a further 2× with ethyl acetate, and the combined organic phases are dried using sodium sulfate, filtered and evaporated to dryness. The residue is purified by means of RP-HPLC, giving tert-butyl 4-[6′-amino-5′-(6-methoxy-1H-benzimidazol-2-yl)-[3,3′]bipyridinyl-6-yl]-piperazine-1-carboxylate.

Workup

  1. additionfilled microwave vessel
  2. customThe reaction solution is irradiated with microwaves for 30 min at 120° C. in the Biotage SmithSynthesizer
  3. filtrationfiltered
  4. extractionThe aqueous phase is extracted a further 2× with ethyl acetate
  5. customthe combined organic phases are dried
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe residue is purified by means of RP-HPLC

Sources & evidence

ORD record
ord-e57988e3075c4a41a59a9ca367f3556f
Source dataset
uspto-grants-2014_02
Patent number
US08648201B2

Reaction notes

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