Dabco → 7-Benzyl-6-oxo-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester

HRID 902526Notes

Reaction equation

HRID 902526 reaction equation
C(Cl)(=O)C(Cl)=O.[CH2:7]([O:9][C:10]([C:12]1[C:17](=[O:18])[N:16]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:15]2[S:26][CH:27]=[CH:28][C:14]=2[C:13]=1O)=[O:11])[CH3:8].[N:30]1([C:36]([C:38]2[S:39][CH:40]=[CH:41][CH:42]=2)=[O:37])[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1.C1N2CCN(CC2)C1.[Cl-].[NH4+]>CN(C=O)C.[Cl-].[Na+].O.O>[CH2:7]([O:9][C:10]([C:12]1[C:17](=[O:18])[N:16]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:15]2[S:26][CH:27]=[CH:28][C:14]=2[C:13]=1[N:33]1[CH2:34][CH2:35][N:30]([C:36]([C:38]2[S:39][CH:40]=[CH:41][CH:42]=2)=[O:37])[CH2:31][CH2:32]1)=[O:11])[CH3:8]

Participants

9

Reactant 5

HCID 9237DabcoHCID 25517Ammonium ChlorideHCID 65578Oxalyl chlorideHCID 7975621-(Thien-2-ylcarbonyl)piperazineHCID 689346847-Benzyl-4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester

Product 1

HCID 118526997-Benzyl-6-oxo-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl esterYield 21%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-45 °C

Procedure

Oxalyl chloride (0.66 mL, 0.008 mol) was added slowly to a solution of 7-benzyl-4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester (60) (1.0 g, 0.003 mol) in 25 mL anhydrous DMF stirred at −45° C. under argon. The solution was heated to 70° C. for 4 hours, and then poured into water. A small amount of brine was added, and the precipitated solid was collected by vacuum filtration. The oily solid was dissolved in dichloromethane, dried with magnesium sulfate, and then concentrated under vacuum to yield an oil. The oil was dissolved in DMF. Piperazin-1-yl-thiophen-2-yl-methanone (1.2 g, 0.004 mol) and DABCO (0.68 g, 0.006 mol) were added to the solution under argon. The solution was heated to 110° C. for 5 hours, and then poured into a 5% ammonium chloride aqueous solution. The precipitated solid was collected by vacuum filtration, and then purified by reverse phase (MeCN/water) chromatography to yield 0.320 g (21%) of 7-benzyl-6-oxo-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester. 1H-NMR (DMSO-d6) δ 1.28 (t, J=7.2 Hz, 3H), 3.40 (b, 4H), 3.81 (b, 4H), 4.26 (q, J=7.2 Hz, 2H), 5.26 (s, 2H), 7.15 (m, 1H), 7.28 (m, 5H), 7.35 (m, 2H), 7.47 (m, 1H), 7.79 (m, 1H) ppm; EIMS m/z 508 (M+1).

Workup

  1. temperatureThe solution was heated to 70° C. for 4 hours
  2. filtrationthe precipitated solid was collected by vacuum filtration
  3. dissolutionThe oily solid was dissolved in dichloromethane
  4. dry with materialdried with magnesium sulfate
  5. concentrationconcentrated under vacuum
  6. customto yield an oil
  7. temperatureThe solution was heated to 110° C. for 5 hours
  8. filtrationThe precipitated solid was collected by vacuum filtration
  9. custompurified by reverse phase (MeCN/water) chromatography

Sources & evidence

ORD record
ord-b46706035edc4ebf959b7cc5889501d4
Source dataset
uspto-grants-2008_04
Patent number
US07365200B2

Reaction notes

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