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

HRID 902534Notes

Reaction equation

HRID 902534 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:11](=[O:12])[N:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)[C:9]2[S:21][C:22]([CH3:24])=[CH:23][C:8]=2[C:7]=1Cl)=[O:5])[CH3:2].[N:26]1([C:32]([C:34]2[S:35][CH:36]=[CH:37][CH:38]=2)=[O:33])[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.C1N2CCN(CC2)C1.[Cl-].[NH4+]>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:11](=[O:12])[N:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)[C:9]2[S:21][C:22]([CH3:24])=[CH:23][C:8]=2[C:7]=1[N:29]1[CH2:30][CH2:31][N:26]([C:32]([C:34]2[S:35][CH:36]=[CH:37][CH:38]=2)=[O:33])[CH2:27][CH2:28]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 9237DabcoHCID 25517Ammonium ChlorideHCID 7975621-(Thien-2-ylcarbonyl)piperazineHCID 597020794-Chloro-7-(3-fluoro-benzyl)-2-methyl-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester

Product 1

HCID 115048137-(3-Fluoro-benzyl)-2-methyl-6-oxo-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl esterYield 65.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-chloro-7-(3-fluoro-benzyl)-2-methyl-6-oxo-6,7-dihydro-thieno[2,3-b]pyrdine-5-carboxylic acid ethyl ester (70) (3.0 g, 7.89 mmol), piperazin-1-yl-thiophen-2-yl-methanone (1.78 g, 9.09 mmol), and DABCO (1.02 g, 9.09 mmol) in anhydrous DMF was heated overnight at 110° C. The solution was cooled and poured into a 2% ammonium chloride aqueous solution. The precipitated solid was collected by vacuum filtration. The solid was redissolved in dichloromethane and filtered. The filtrate was concentrated under vacuum and the residue was purified by flash chromatography eluting with 0-5% MeOH in CH2Cl2 gradient to yield 2.8 g (65%) of 7-(3-fluoro-benzyl)-2-methyl-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 1.29 (t, J=7.2 Hz, 3H), 2.43 (s, 3H), 3.29 (m, 4H), 3.81 (m, 4H), 4.26 (q, J=7.2 Hz, 2H), 5.23 (s, 2H), 6.99 (d, J=1.2 Hz, 1H), 7.06-7.16 (m, 4H), 7.41 (m, 1H), 7.46 (dd, J=1.2, 4.0 Hz, 1H), 7.79 (dd, J=1.2, 4.8 Hz, 1H); EIMS m/z 540(M+1).

Workup

  1. temperatureThe solution was cooled
  2. filtrationThe precipitated solid was collected by vacuum filtration
  3. dissolutionThe solid was redissolved in dichloromethane
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under vacuum
  6. customthe residue was purified by flash chromatography
  7. washeluting with 0-5% MeOH in CH2Cl2 gradient

Sources & evidence

ORD record
ord-71b05e80bf944e9dbba6b1e12a96491b
Source dataset
uspto-grants-2008_04
Patent number
US07365200B2

Reaction notes

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