Dimethylformamide → HCID 178522941, compound

HRID 2299315Notes

Reaction equation

HRID 2299315 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.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN([CH:68]=[O:69])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:68]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[O:69])[S:16][C:13]3=[N:14][CH:15]=2)=[O:9])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8083MorpholineHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 178522942HCID 178522942, compound

Product 1

HCID 178522941HCID 178522941, compoundYield 33%

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 (2.00 g) from Example No. 2 in DMF (45 mL) are added triethylamine (1.25 mL), morpholine (15.7 mL), Pd(OAc)2 (0.101 g), and dppp (0.186 g). The reaction mixture is degassed by bubbling N2 through the solution for 15 minutes. Carbon monoxide is then bubbled through the solution, and the reaction mixture is heated to 70° C. and stirred for 18 h. The reaction mixture is allowed to cool to room temperature and water (25 mL) and 2 N HCl (75 mL) are added. The resulting green solid is filtered off and the filtrate is extracted with CH2Cl2 (4×100 mL). The combined organic layers are dried with MgSO4, filtered, and concentrated in vacuo. The resulting orange oil is purified by column chromatography (CH2Cl2; CH2Cl2/methanol, 98/2). The resulting pale yellow solid is recrystallized from acetonitrile to yield 0.648 g (33%) of the title compound as an off-white solid.

Workup

  1. customThe reaction mixture is degassed
  2. customby bubbling N2 through the solution for 15 minutes
  3. customCarbon monoxide is then bubbled through the solution
  4. temperatureto cool to room temperature
  5. additionwater (25 mL) and 2 N HCl (75 mL) are added
  6. filtrationThe resulting green solid is filtered off
  7. extractionthe filtrate is extracted with CH2Cl2 (4×100 mL)
  8. dry with materialThe combined organic layers are dried with MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe resulting orange oil is purified by column chromatography (CH2Cl2; CH2Cl2/methanol, 98/2)
  12. customThe resulting pale yellow solid is recrystallized from acetonitrile

Sources & evidence

ORD record
ord-c1f1696290f54ffb8f0a13dbf595d9d0
Source dataset
uspto-grants-2002_12
Patent number
US06495683B2

Reaction notes

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