Sodium Carbonate → HCID 15950088, compound

HRID 2220460Notes

Reaction equation

HRID 2220460 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:20]1[CH:25]=[C:24](B(O)O)[CH:23]=[N:22][CH:21]=1.C([O-])([O-])=O.[Na+].[Na+].[CH3:35][O:36][C:37]([C:39]1[N:40]([CH2:60][CH2:61][F:62])[CH:41]=[C:42]([C:44]2([C:52]3[CH:57]=[CH:56][C:55]([F:58])=[C:54](Br)[CH:53]=3)[C:48](=[O:49])[N:47]([CH3:50])[C:46]([NH2:51])=[N:45]2)[CH:43]=1)=[O:38]>C(Cl)(Cl)Cl.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].CO.CCOC(C)=O.CCOC(C)=O.C1(C)C=CC=CC=1.CO>[CH3:35][O:36][C:37]([C:39]1[N:40]([CH2:60][CH2:61][F:62])[CH:41]=[C:42]([C:44]2([C:52]3[CH:57]=[CH:56][C:55]([F:58])=[C:54]([C:24]4[CH:25]=[N:20][CH:21]=[N:22][CH:23]=4)[CH:53]=3)[C:48](=[O:49])[N:47]([CH3:50])[C:46]([NH2:51])=[N:45]2)[CH:43]=1)=[O:38]

Participants

11

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 59772744HCID 59772744, compound

Product 1

HCID 15950088HCID 15950088, compoundYield 65.2%

Reagents, catalysts & solvents 6

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 1140TolueneSolventHCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

In a pressure tube was put 2 mL of MeOH and 2 mL of toluene. The solution was degassed with argon and 7.5 mg (0.008 mmol) of Pd2(dba)3 and 8.6 mg of triphenylphosphine was added under an argon atmosphere. After 15 min stirring at room temperature, 47.0 mg (0.38 mmol) of 5-pyrimidyl-boronic acid, 83 mg (0.78 mmol) of Na2CO3, and 125 mg (0.27 mmol) of 4-[2-Amino-4-(3-bromo-4-fluoro-phenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoro-ethyl)-1H-pyrrole-2-carboxylic acid methyl ester was added and the reaction sealed heated to 110° C. for 18 h. The reaction mixture was cooled, diluted with 100 mL of CHCl3, filtered through celite and the solvent removed at reduced pressure. Chromatography on silica gel using a gradient of EtOAc to 2%-8% MeOH-EtOAc yielded 0.08 gm (64% yield) of a white solid (mp 88-90° C.). 1H NMR (500 MHz, CDCl3) δ: 3.15 (s, 3H), 3.73 (s, 3H), 4.50 (m, 1H), 4.58 (m, 2H), 4.68 (m, 1H), 6.96 (s, 2H), 7.16 (t, 1H, J=8.66 Hz), 7.65 (m, 2H), 8.88 (m, 2H), 9.15 (s, 1H). MS (ESI) m/z 455.1 ([M+H])+; MS (ESI) m/z 453.1 ([M−H])−.

Workup

  1. customIn a pressure tube was put
  2. additionwas added under an argon atmosphere
  3. customthe reaction sealed
  4. temperatureheated to 110° C. for 18 h
  5. temperatureThe reaction mixture was cooled
  6. filtrationfiltered through celite
  7. customthe solvent removed at reduced pressure

Sources & evidence

ORD record
ord-dbf851f25a864a458f1c23eb27059c8b
Source dataset
uspto-grants-2008_08
Patent number
US07417047B2

Reaction notes

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