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 1169250Notes

Reaction equation

HRID 1169250 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%). 1H NMR (300 mHz, CD3OD) δ7.15 (m, 2H), 6.98 (m, 2H), 4.21 (q, J=8.1 Hz, 1H), 3.68 (m, 4H), 3.49 (dd, J=13.6, 8.1 Hz, 1H), 3.35 (m, 1H), 3.25 (t, J=6.6 Hz, 2H), 2.98 (m, 2H), 2.78 (m, 2H), 2.6-2.4 (11H), 2.07 (m, 1H), 1.9-1.5 (5H), 0.98 (m, 1H), ESI MS: (M+H)+=497.1.

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-e44576afd5bf43798963cd860eacb073
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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