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

HRID 902497Notes

Reaction equation

HRID 902497 reaction equation
[CH:1]([O:4][C:5]([C:7]1[C:12](=[O:13])[N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[C:10]2[CH:22]=[CH:23][S:24][C:9]=2[C:8]=1[N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)=[O:6])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.C(N(CC)CC)C.[F:60][C:61]1[S:65][C:64]([C:66](O)=[O:67])=[CH:63][CH:62]=1.C([O-])(O)=O.[Na+]>>[CH:1]([O:4][C:5]([C:7]1[C:12](=[O:13])[N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[C:10]2[CH:22]=[CH:23][S:24][C:9]=2[C:8]=1[N:25]1[CH2:26][CH2:27][N:28]([C:66]([C:64]2[S:65][C:61]([F:60])=[CH:62][CH:63]=2)=[O:67])[CH2:29][CH2:30]1)=[O:6])([CH3:3])[CH3:2]

Participants

7

Reactant 6

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 118049015-fluorothiophene-2-carboxylic acidHCID 59740501HCID 59740501, compound

Product 1

HCID 693161304-(3-Fluoro-benzyl)-7-[4-(5-fluoro-thiophene-2-carbonyl)-piperazin-1-yl]-5-oxo-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid isopropyl esterYield 83.3%

Procedure

A solution of 4-(3-fluoro-benzyl)-5-oxo-7-piperazin-1-yl-4,5-dihydro-thieno[3,2-b]pyrdine-6-carboxylic acid isopropyl ester (20) (2 g, 4.65 mmol), HOBt (0.692 g, 5.12 mmol), EDC.HCl (0.982 g, 5.12), triethylamine (0.971 mL, 6.98 mmol) and 5-fluoro-thiophene-2-carboxylic acid (0.749 g, 5.12 mmol) was stirred overnight at room temperature. The solution was poured into 2.5% NaHCO3 solution and the solids formed were filtered, washed by cold water and air dried. The crude product was purified by flash chromatography eluting with 0-10% methanol in CH2Cl2 gradient to yield 2.16 g (83%) of 4-(3-fluoro-benzyl)-7-[4-(5-fluoro-thiophene-2-carbonyl)-piperazin-1-yl]-5-oxo-4,5-dihydro-thieno[3,2-b]pyrdine-6-carboxylic acid isopropyl ester. 1H-NMR (DMSO-d6) δ 1.29 (d, J=6.0 Hz, 6H), 3.37 (m, 4H), 3.79 (m, 4H), 5.10 (m, 1H), 5.38 (s, 2H), 6.80 (m, 1H), 7.07 (m, 3H), 7.28 (t, J=3.6 Hz, 1H), 7.32 (d, J=5.6 Hz, 1H), 7.37 (m, 1H), 8.02 (d, J=5.6 Hz, 1H); EIMS m/z 558 (M+1).

Workup

  1. customthe solids formed
  2. filtrationwere filtered
  3. washwashed by cold water and air
  4. customdried
  5. customThe crude product was purified by flash chromatography
  6. washeluting with 0-10% methanol in CH2Cl2 gradient

Sources & evidence

ORD record
ord-2ced7f0374554381ba693ea7c8d5cc49
Source dataset
uspto-grants-2008_04
Patent number
US07365200B2

Reaction notes

Loading…