Sodium hydride → HCID 59702051, compound

HRID 902485Notes

Reaction equation

HRID 902485 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:11](=[O:12])[NH:10][C:9]2[CH:13]=[CH:14][S:15][C:8]=2[C:7]=1[N:16]1[CH2:21][CH2:20][N:19]([C:22]([C:24]2[S:25][CH:26]=[CH:27][CH:28]=2)=[O:23])[CH2:18][CH2:17]1)=[O:5])[CH3:2].[H-].[Na+].[F:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36]Br)=[CH:34][CH:33]=1>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:11](=[O:12])[N:10]([CH2:36][C:35]2[CH:38]=[CH:39][C:32]([F:31])=[CH:33][CH:34]=2)[C:9]2[CH:13]=[CH:14][S:15][C:8]=2[C:7]=1[N:16]1[CH2:21][CH2:20][N:19]([C:22]([C:24]2[S:25][CH:26]=[CH:27][CH:28]=2)=[O:23])[CH2:18][CH2:17]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 59702095HCID 59702095, compound

Product 1

HCID 59702051HCID 59702051, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-oxo-7-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid ethyl ester (5) (232 mg, 0.55 mmol) in dry DMF was added to a suspension of NaH (60% in mineral oil, 24 mg, 0.61 mmol) at room temperature. The solution was stirred at room temperature for 15 min. 4-Fluorobenzylbromide (76 μL, 0.61 mmol) was added to the solution through a syringe and further stirred at room temperature for 1 h. The solution was poured into ice water and the solids formed were filtered, washed by cold water, and dried. The crude product was purified by flash chromatography eluting with 0-2% methanol in CH2Cl2 gradient to yield 207 mg (90%) of 4-(4-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 as white solids. 1H NMR (400 MHz, DMSO-d6) δ 1.28 (t, J=7.2 Hz, 3H), 3.34 (m, 4H), 3.80 (m, 4H), 4.27 (q, J=7.2 Hz, 2H), 5.34 (s, 2H), 7.14-7.18 (m, 3H), 7.29-7.35 (m, 3H), 7.48 (dd, J=1.2, 3.6, Hz, 1H), 7.80 (dd, J=1.2, 5.2 Hz, 1H), 8.04 (d, J=5.6 Hz, 1H) ppm; MS m/z=526 amu (M++1). Anal. (C26H24FN3O4S2) C, H, N.

Workup

  1. stirringfurther stirred at room temperature for 1 h
  2. customthe solids formed
  3. filtrationwere filtered
  4. washwashed by cold water
  5. customdried
  6. customThe crude product was purified by flash chromatography
  7. washeluting with 0-2% methanol in CH2Cl2 gradient

Sources & evidence

ORD record
ord-a428de21e4f34db8863d5935ade80042
Source dataset
uspto-grants-2008_04
Patent number
US07365200B2

Reaction notes

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