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

HRID 902499Notes

Reaction equation

HRID 902499 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[CH:21]=[CH:22][S:23][C:8]=2[C:7]=1Cl)=[O:5])[CH3:2].N12CCN(CC1)CC2.[N:33]1([C:39]([C:41]2[S:42][CH:43]=[CH:44][CH:45]=2)=[O:40])[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.[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[CH:21]=[CH:22][S:23][C:8]=2[C:7]=1[N:36]1[CH2:37][CH2:38][N:33]([C:39]([C:41]2[S:42][CH:43]=[CH:44][CH:45]=2)=[O:40])[CH2:34][CH2:35]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 9237DabcoHCID 25517Ammonium ChlorideHCID 7975621-(Thien-2-ylcarbonyl)piperazineHCID 693126547-Chloro-4-(3-fluoro-benzyl)-5-oxo-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid ethyl ester

Product 1

HCID 118526974-(3-Fluoro-benzyl)-5-oxo-7-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid ethyl esterYield 91%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 7-chloro-4-(3-fluoro-benzyl)-5-oxo-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid ethyl ester (17) (45 g, 123 mmol), 1,4-diazabicyclo[2.2.2]octane (15.9 g, 141 mmol) and piperazin-1-yl-thiophene-2-yl-methanone (27.8 g, 141 mmol) in dry DMF was heated at 110° C. for 7 h under argon. The solution was cooled and poured into 2% ammonium chloride solution. The solids formed were filtered and washed by cold water. The solids were dissolved in dichloromethane and washed by water. The organic phase was dried over MgSO4 and concentrated under vacuum to yield 58.6 g (91%) of 4-(3-fluoro-benzyl)-5-oxo-7-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid ethyl ester. 1H-NMR (DMSO-d6): δ 1.29 (t, J=7.2 Hz, 3H), 3.37 (m, 4H), 3.82 (m, 4H), 4.27 (q, J=7.2 Hz, 2H), 5.38 (s, 2H), 7.05-7.16 (m, 4H), 7.33 (d, J=5.6 Hz, 1H), 7.36 (m, 1H), 7.48 (dd, J=1.2, 3.6 Hz, 1H), 7.79 (dd, J=1.2, 5.2 Hz, 1H), 8.03 (d, J=5.6 Hz, 1H); EIMS m/z 526 (M+1). Anal. (C26H24FN3O4S2) C, H, N.

Workup

  1. temperatureThe solution was cooled
  2. customThe solids formed
  3. filtrationwere filtered
  4. washwashed by cold water
  5. dissolutionThe solids were dissolved in dichloromethane
  6. washwashed by water
  7. dry with materialThe organic phase was dried over MgSO4
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-787b65a316974237a94fadfbe367b7af
Source dataset
uspto-grants-2008_04
Patent number
US07365200B2

Reaction notes

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