Sodium Carbonate → HCID 57417075, compound

HRID 1430120Notes

Reaction equation

HRID 1430120 reaction equation
I[C:2]1[S:6][C:5]([NH:7][C:8](=[O:10])[CH3:9])=[N:4][C:3]=1[CH3:11].[N:12]1([C:17]2[N:22]=[C:21](B3OC(C)(C)C(C)(C)O3)[CH:20]=[CH:19][CH:18]=2)[CH:16]=[CH:15][N:14]=[CH:13]1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[N:12]1([C:17]2[N:22]=[C:21]([C:2]3[S:6][C:5]([NH:7][C:8](=[O:10])[CH3:9])=[N:4][C:3]=3[CH3:11])[CH:20]=[CH:19][CH:18]=2)[CH:16]=[CH:15][N:14]=[CH:13]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 457858982-(1H-Imidazol-1-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 57417074N-(5-Iodo-4-methyl-2-thiazolyl)acetamide

Product 1

HCID 57417075HCID 57417075, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of N-(5-iodo-4-methyl-thiazol-2-yl)-acetamide (312 mg), 6-(imidazol-1-yl)pyridine-2-boronic acid pinacol ester (600 mg), 1,1′-bis(diphenylphosphino)ferrocene-dichloropalladium (II) (45 mg) and sodium carbonate (594 mg) in DME (3.1 ml) and water (3.1 ml) is heated in a Emrys Optimiser personal chemistry microwave at 85° C. for 45 minutes. Water is added (5 ml) and the mixture extracted with 3×10% methanol in CH2Cl2, the combined organic layers evaporated and purified by reversed phase chromatography (Method B) collecting the 12.8 minute retention time component. Partial evaporation of the fractions, neutralization with NaHCO3, extraction with 10% methanol in CH2Cl2 (5×) and evaporation gives a white solid. Further purification of this material by normal phase chromatography on silica gel eluting with a gradient from EtOAc to 10% methanol in EtOAc gives the title compound as a white solid. Hplc/MS (Method C) RT 1.31 minutes, M+H 299.9 and M−H 298.0.

Workup

  1. extractionthe mixture extracted with 3×10% methanol in CH2Cl2
  2. customthe combined organic layers evaporated
  3. custompurified by reversed phase chromatography (Method B)
  4. customcollecting the 12.8 minute retention time component
  5. customPartial evaporation of the fractions, neutralization
  6. extractionwith NaHCO3, extraction
  7. customwith 10% methanol in CH2Cl2 (5×) and evaporation
  8. customgives a white solid
  9. customFurther purification of this material by normal phase chromatography on silica gel eluting with a gradient from EtOAc to 10% methanol in EtOAc

Sources & evidence

ORD record
ord-f7db861608a747388f0ee1b1c1772c36
Source dataset
uspto-grants-2015_01
Patent number
US08940771B2

Reaction notes

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