1-Butanol → 4-[4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-2-oxo-piperazin-1-ylmethyl]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carboxylic acid

HRID 1433094Notes

Reaction equation

HRID 1433094 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:9]=[C:8]([S:10]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)[C:15](=[O:26])[CH2:14]3)(=[O:12])=[O:11])[S:7][C:6]=2[CH:27]=1.Cl[C:29]1[CH:37]=[CH:36][C:32]([C:33](N)=[O:34])=[CH:31][N:30]=1.C(N(C(C)C)CC)(C)C.C([OH:51])CCC>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:9]=[C:8]([S:10]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH:20]4[CH2:21][CH2:22][N:23]([C:29]5[CH:37]=[CH:36][C:32]([C:33]([OH:51])=[O:34])=[CH:31][N:30]=5)[CH2:24][CH2:25]4)[C:15](=[O:26])[CH2:14]3)(=[O:12])=[O:11])[S:7][C:6]=2[CH:27]=1

Participants

5

Reactant 4

HCID 2631-ButanolHCID 804566-ChloronicotinamideHCID 81531DiisopropylethylamineHCID 670148114-(6-Chloro-benzo[b]thiophene-2-sulfonyl)-1-piperidin-4-ylmethyl-piperazin-2-one

Product 1

HCID 670147354-[4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-2-oxo-piperazin-1-ylmethyl]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carboxylic acid

Conditions

Temperature
110 °C

Procedure

To a solution of 4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-1-piperidin-4-ylmethyl-piperazin-2-one (20 mg, 0.047 mmol) in n-butanol (0.5 mL) is added 6-chloronicotinamide (15 mg, 0.094 mmole) and diisopropylethylamine (0.016 mL, 0.094 mmole) and heated at 110° C. 16 h. The reaction is concentrated and purified by column chromatography (silica, 20% methanol/dichloromethane) to provide 4-[4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-2-oxo-piperazin-1-ylmethyl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carboxylic acid. 1H NMR (300 MHz, CD3OD) δ 8.59 (d, 1H), 8.11-7.92 (m, 3H), 7.54 (dd, 1H), 6.72 (d, 1H), 4.27 (d, 1H), 3.92 (s, 2H), 3.57-3.47 (m, 4H), 3.25 (d, 2H), 2.79-2.71 (dt, 2H), 1.96-1.80 (m, 1H), 1.50 (d, 2H), 1.29-1.06 (m, 2H); MS (Ion spray) 549 (M+H)+.

Workup

  1. custom16 h
  2. concentrationThe reaction is concentrated
  3. custompurified by column chromatography (silica, 20% methanol/dichloromethane)

Sources & evidence

ORD record
ord-6bcfc8bc7fef4775b0f911081312d0cf
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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