Diisopropylethylamine → 5-[(1R)-2-{4-[2-(1,1-dioxido-1-benzothiophen-5-yl)-2-oxoethyl]piperazin-1-yl}-1-hydroxyethyl]-4-methyl-2-benzofuran-1 (3H)-one

HRID 2281357Notes

Reaction equation

HRID 2281357 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]2[S:12](=[O:14])(=[O:13])[CH:11]=[CH:10][C:9]=2[CH:15]=1)=[O:4].Cl.[C@@H:17]12[N:24]([CH2:25][C@@H:26]([C:28]3[C:29]([CH3:38])=[C:30]4[C:34](=[CH:35][CH:36]=3)[C:33](=[O:37])[O:32][CH2:31]4)[OH:27])[C@@H:21](CC1)[CH2:20][NH:19][CH2:18]2.C(N(CC)C(C)C)(C)C>C1COCC1>[O:13]=[S:12]1(=[O:14])[C:8]2[CH:7]=[CH:6][C:5]([C:3](=[O:4])[CH2:2][N:19]3[CH2:18][CH2:17][N:24]([CH2:25][C@@H:26]([C:28]4[CH:36]=[CH:35][C:34]5[C:33](=[O:37])[O:32][CH2:31][C:30]=5[C:29]=4[CH3:38])[OH:27])[CH2:21][CH2:20]3)=[CH:15][C:9]=2[CH:10]=[CH:11]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 895433782-Bromo-1-(1,1-dioxido-1-benzothiophen-5-yl)ethanoneHCID 1176421655-((R)-2-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-1-hydroxyethyl)-4-methylisobenzofuran-1(3H)-one hydrochloride2×

Product 1

HCID 1176419265-[(1R)-2-{4-[2-(1,1-dioxido-1-benzothiophen-5-yl)-2-oxoethyl]piperazin-1-yl}-1-hydroxyethyl]-4-methyl-2-benzofuran-1 (3H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-bromo-1-(1,1-dioxido-1-benzothiophen-5-yl)ethanone (50 mg, 0.17 mmol) in 1.0 mL THF and 5-[(1R)-1-hydroxy-2-(piperazin-1-yl)ethyl]-4-methyl-2-benzofuran-1(3H)-one hydrochloride (INTERMEDIATE 12) (61 mg, 0.17 mmol) was added N,N-diisopropylethylamine (0.70 mmol, 120 μL) and allowed to stir at ambient temperature for 2 hours. The reaction was quenched by the addition of water and extracted three times with ethyl acetate (10 mL). The combined organic layers were then dried over sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified via MPLC (10% DCM/MeOH) to afford 5-[(1R)-2-{4-[2-(1,1-dioxido-1-benzothiophen-5-yl)-2-oxoethyl]piperazin-1-yl}-1-hydroxyethyl]-4-methyl-2-benzofuran-1 (3H)-one.

Workup

  1. customThe reaction was quenched by the addition of water
  2. extractionextracted three times with ethyl acetate (10 mL)
  3. dry with materialThe combined organic layers were then dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified via MPLC (10% DCM/MeOH)

Sources & evidence

ORD record
ord-bef1ceda6f474563b17aae3abf759e5a
Source dataset
uspto-grants-2015_09
Patent number
US09139585B2

Reaction notes

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