Triethylamine → 1-{(3S,4S)-4-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-1,1-dioxo-tetrahydrothiophen-3-yl}-3-(2-morpholin-4-yl-ethyl)-urea, bis-hydrochloride salt

HRID 497501Notes

Reaction equation

HRID 497501 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][C@@H:7]2[CH2:12][CH2:11][CH2:10][N:9]([CH2:13][C@@H:14]3[CH2:18][S:17](=[O:20])(=[O:19])[CH2:16][C@H:15]3[NH2:21])[CH2:8]2)=[CH:4][CH:3]=1.[ClH:24].[N+](C1C=CC([O:34][C:35](=O)[NH:36][CH2:37][CH2:38][N:39]2[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)=CC=1)([O-])=O.C(N(CC)CC)C>CN(C)C=O>[ClH:24].[ClH:24].[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C@@H:7]2[CH2:12][CH2:11][CH2:10][N:9]([CH2:13][C@@H:14]3[CH2:18][S:17](=[O:19])(=[O:20])[CH2:16][C@H:15]3[NH:21][C:35]([NH:36][CH2:37][CH2:38][N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)=[O:34])[CH2:8]2)=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 69747847(2-Morpholin-4-yl-ethyl)-carbamic acid 4-nitro-phenyl ester hydrochlorideHCID 69747909(3S,4S)-4-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-1,1-dioxo-tetrahydro-thiophen-3-ylamine

Product 1

HCID 1317240851-{(3S,4S)-4-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-1,1-dioxo-tetrahydrothiophen-3-yl}-3-(2-morpholin-4-yl-ethyl)-urea, bis-hydrochloride saltYield 149.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(3S,4S)-4-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-1,1-dioxo-tetrahydrothiophen-3-ylamine (47 mg, 137 μmol) and (2-morpholin-4-yl-ethyl)-carbamic acid 4-nitro-phenyl ester hydrochloride (55 mg, 164 μmol) were dissolved in N,N-dimethylformamide (1 mL) and treated with triethylamine (23 μL, 164 μmol). The mixture was stirred at room temperature for 67 h, and then concentrated. The residue was purified by flash column chromatography (3% methanol/dichloromethane containing 0.3% aqueous ammonium hydroxide). After isolation, the product was dissolved in 1N hydrochloric acid and water and lyophilized to provide a fluffy white solid (70 mg, 90%).

Workup

  1. concentrationconcentrated
  2. customThe residue was purified by flash column chromatography (3% methanol/dichloromethane containing 0.3% aqueous ammonium hydroxide)
  3. dissolutionAfter isolation, the product was dissolved in 1N hydrochloric acid

Sources & evidence

ORD record
ord-0497a8eb4d874e80b5fedd0040d68db4
Source dataset
uspto-grants-2005_09
Patent number
US06949546B2

Reaction notes

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