Methanol → HCID 178496975, compound

HRID 2299303Notes

Reaction equation

HRID 2299303 reaction equation
[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11]([OH:20])=[C:12]3[CH:18]=[C:17](I)[S:16][C:13]3=[N:14][CH:15]=2)=[O:9])=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:30][OH:31].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN([CH:64]=[O:65])C>CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11]([OH:20])=[C:12]3[CH:18]=[C:17]([C:30]([O:65][CH3:64])=[O:31])[S:16][C:13]3=[N:14][CH:15]=2)=[O:9])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 178522942HCID 178522942, compound

Product 1

HCID 178496975HCID 178496975, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

To a solution of N-(4-chlorobenzyl)-4-hydroxy-2-iodothieno[2,3-b]pyridine-5-carboxamide (2.61 g) from Example No. 2 in DMF (33 mL) are added triethylamine (1.6 mL), methanol (9.5 mL), Pd(OAc)2(0.132 g), and dppp (0.242 g). Carbon monoxide is bubbled through the solution, and the reaction is heated to 70° C. The reaction is stirred at 70° C. for 18 h. The reaction mixture is cooled to rt, and water (25 mL) and 2 N HCl (25 mL) are added. The resulting precipitate is filtered off and purified by column chromatography (CH2Cl2; CH2Cl2/methanol, 99/1; 98/2). A mixture of starting material and desired product is isolated as a yellow solid. This material is re-subjected to the reaction conditions above. The reaction is stirred at 70° C. for 18 h. The reaction is cooled to rt and water (25 mL) and 2 N HCl (25 mL) are added. The resulting orange solid is filtered off and purified by column chromatography (CH2Cl2; CH2Cl2/methanol, 99/1; 98/2). Fractions homogeneous by TLC are combined and concentrated in vacuo to yield a pale yellow solid which is recrystallized from methanol to yield 1.337 g (60%) of the title compound as a pale yellow, crystalline solid.

Workup

  1. customCarbon monoxide is bubbled through the solution
  2. temperatureThe reaction mixture is cooled to rt
  3. additionwater (25 mL) and 2 N HCl (25 mL) are added
  4. filtrationThe resulting precipitate is filtered off
  5. custompurified by column chromatography (CH2Cl2; CH2Cl2/methanol, 99/1; 98/2)
  6. additionA mixture of starting material

Sources & evidence

ORD record
ord-2d78c9789ac64f6eae827e6290d49cef
Source dataset
uspto-grants-2002_12
Patent number
US06495683B2

Reaction notes

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