Sodium Carbonate → HCID 23653918, compound

HRID 1785499Notes

Reaction equation

HRID 1785499 reaction equation
C[O:2][C:3]([C:5]1[S:9][C:8]([N:10]2[C:14]3[CH:15]=[C:16]([O:21][CH3:22])[C:17]([O:19][CH3:20])=[CH:18][C:13]=3[N:12]=[CH:11]2)=[N:7][C:6]=1Br)=[O:4].[CH3:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.C([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CO.O.C1COCC1>[CH3:20][O:19][C:17]1[C:16]([O:21][CH3:22])=[CH:15][C:14]2[N:10]([C:8]3[S:9][C:5]([C:3]([OH:2])=[O:4])=[C:6]([C:28]4[CH:29]=[CH:30][C:25]([CH3:24])=[CH:26][CH:27]=4)[N:7]=3)[CH:11]=[N:12][C:13]=2[CH:18]=1

Participants

10

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 79799Tolylboronic acidHCID 57595851HCID 57595851, compound

Product 1

HCID 23653918HCID 23653918, compoundYield 53.4%

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-bromo-2-(5,6-dimethoxy-benzoimidazol-1-yl)-thiazole-5-carboxylic acid methyl ester (40 mg, 0.1 mmol), 4-methylphenylboronic acid (20.4 mg, 0.15 mmol) in ethylene glycol dimethyl ether (1 ml) was added Na2CO3 (2M, 100 μL, 0.2 mmol) and [1,1′-bis(diphenylphosphino)-ferrocene]dichloro palladium(II) (4 mg, 0.005 mmol). The mixture was heated to 100° C. for 3 hrs. The solvent was evaporated and 2 ml water was added. It was then extracted with 2×3 ml EtOAc. The combined organics were concentrated in vacuo. To this crude was added THF (0.5 ml), water (0.5 ml), methanol (0.2 ml) and NaOH (20 mg, 0.05 mmol). The mixture was heated to 60° C. for 3 hrs. The solvents were evaporated and the crude was purified by prep-HPLC to afford 2-(5,6-Dimethoxy-benzoimidazol-1-yl)-4-p-tolyl-thiazole-5-carboxylic acid (21.1 mg, 53%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.57 (br.s., 1H); 8.82 (s, 1 H); 7.83 (m, 3 H); 7.39 (s, 1 H); 7.31 (d, 2 H); 3.86 (s, 3 H); 3.85(s, 3 H), 2.39 (s, 3H). MS m/z 396 (M+1).

Workup

  1. customThe solvent was evaporated
  2. addition2 ml water was added
  3. extractionIt was then extracted with 2×3 ml EtOAc
  4. concentrationThe combined organics were concentrated in vacuo
  5. temperatureThe mixture was heated to 60° C. for 3 hrs
  6. customThe solvents were evaporated
  7. customthe crude was purified by prep-HPLC

Sources & evidence

ORD record
ord-97e1be71531e4514a0017251a3ba16db
Source dataset
uspto-grants-2009_03
Patent number
US07504513B2

Reaction notes

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