Ethyl Acetate → HCID 9910299, compound

HRID 2300850Notes

Reaction equation

HRID 2300850 reaction equation
[C:1]1([C@@H:7]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[C:20]4[CH:21]=[CH:22][C:23](I)=[CH:24][C:19]=4[N:18]=[CH:17]3)[CH:13]=[CH:12][N:11]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:26]([O-:29])([O-])=O.[K+].[K+].[S:32]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33]1.C(OCC)(=O)C>C1(OC)C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]1([C@@H:7]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[C:20]4[CH:21]=[CH:22][C:23]([C:26]([C:34]5[CH:35]=[CH:36][S:32][CH:33]=5)=[O:29])=[CH:24][C:19]=4[N:18]=[CH:17]3)[CH:13]=[CH:12][N:11]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 581760Thiophene-3-boronic acidHCID 59924653HCID 59924653, compound

Product 1

HCID 9910299HCID 9910299, compoundYield 10.8%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 7519AnisoleSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-[(S)-1-phenylethylamino]-4-[5-iodobenzimidazol-1-yl]pyrimidine (EXAMPLE 271) (66 mg), K2CO3 (103 mg), 3-thiopheneboronic acid (58 mg) and Pd(PPh3)2Cl2 (1 mg) in anisole (6 mL) was stirred overnight at 100° C. under 1 Atm CO. The reaction mixture was poured into a separatory funnel containing 100 mL ethyl acetate and was washed with water and brine. The organic extracts were combined, dried over anhydrous MgSO4, filtered and concentrated. The product was purified by silica gel chromatography (eluted with a gradient of 100% CH2Cl2 going to 5% MeOH in CH2Cl2) followed by reverse phase chromatography (eluted with a gradient going from 50% water in methanol (with 0.1% TFA) to 100% methanol (with 0.1% TFA)). The resulting salt was then subjected to preparative thin layer chromatography (eluted with 5% (2N NH3 in MeOH) in CH2Cl2) to give 6.9 mg of the title compound. Mass spectrum (ESI): 426.0 (M+1).

Workup

  1. additionThe reaction mixture was poured into a separatory funnel
  2. washwas washed with water and brine
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe product was purified by silica gel chromatography (
  7. washeluted with a gradient of 100% CH2Cl2 going to 5% MeOH in CH2Cl2)
  8. washeluted with a gradient
  9. washThe resulting salt was then subjected to preparative thin layer chromatography (eluted with 5% (2N NH3 in MeOH) in CH2Cl2)

Sources & evidence

ORD record
ord-c1fe92d9baad44d1b6e333a208d7345d
Source dataset
uspto-grants-2002_12
Patent number
US06498165B1

Reaction notes

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