Triethylamine → 1-(5-acetyl-4-methyl-thiazol-2-yl)-3-{(3R,4S)-4-[(S)-3-(4-fluorobenzyl)-piperidine-1-carbonyl]-1,1-dioxo-tetrahydro-1lambda6-thiophen-3-yl}-urea

HRID 1169251Notes

Reaction equation

HRID 1169251 reaction equation
[NH2:1][C@@H:2]1[CH2:6][S:5](=[O:8])(=[O:7])[CH2:4][C@H:3]1[C:9]([N:11]1[CH2:16][CH2:15][CH2:14][C@@H:13]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[CH2:12]1)=[O:10].C1([O:31][C:32](=O)[NH:33][C:34]2[S:35][C:36]([C:40](=[O:42])[CH3:41])=[C:37]([CH3:39])[N:38]=2)C=CC=CC=1.C(N(CC)CC)C>CN(C)C=O>[C:40]([C:36]1[S:35][C:34]([NH:33][C:32]([NH:1][C@@H:2]2[C@@H:3]([C:9]([N:11]3[CH2:16][CH2:15][CH2:14][C@@H:13]([CH2:17][C:18]4[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=4)[CH2:12]3)=[O:10])[CH2:4][S:5](=[O:7])(=[O:8])[CH2:6]2)=[O:31])=[N:38][C:37]=1[CH3:39])(=[O:42])[CH3:41]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 22259036Phenyl (5-acetyl-4-methyl-1,3-thiazol-2-yl)carbamateHCID 69748830[(3R,4S)-4-Amino-1,1-dioxo-tetrahydrothiophen-3-yl]-[(S)-3-(4-fluorobenzyl)-piperidin-1-yl]-methanone

Product 1

HCID 213624291-(5-acetyl-4-methyl-thiazol-2-yl)-3-{(3R,4S)-4-[(S)-3-(4-fluorobenzyl)-piperidine-1-carbonyl]-1,1-dioxo-tetrahydro-1lambda6-thiophen-3-yl}-ureaYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

[(3R,4S)-4-Amino-1,1-dioxo-tetrahydrothiophen-3-yl]-[(S)-3-(4-fluorobenzyl)-piperidin-1-yl]-methanone (50 mg, 141 μmol) and [5-acetyl-4-methylthiazol-2-yl]-carbamic acid phenyl ester (43 mg, 155 μmol) were dissolved in N,N-dimethylformamide (1 mL) and treated with triethylamine (22 μL, 155 μmol). The mixture was stirred at room temperature for 94 h , and then concentrated. The residue was purified by flash column chromatography (4% methanol/dichloromethane containing 0.4% aqueous ammonium hydroxide) to provide a white solid (41 mg, 55%). 1H NMR (300 mHz, CD3OD) δ7.16 (m, 2H), 6.95 (m, 2H), 4.74 (m, 1H), 4.32 (m, 1H), 4.1-3.8 (m, 2H), 3.6-3.5 (m, 2H), 3.4-3.2 (m, 2H), 3.2-2.8 (m, 2H), 2.54 (s, 3H), 2.5 (m, 2H), 2.46+2.44 (2s, 3H), 1.75 (m, 3H), 1.43 (m, 1H), 1.23 (m, 1H), ESI MS: (M+H)+=537.4.

Workup

  1. concentrationconcentrated
  2. customThe residue was purified by flash column chromatography (4% methanol/dichloromethane containing 0.4% aqueous ammonium hydroxide)

Sources & evidence

ORD record
ord-d717eca0bb0e4c0e900a6fef7c524945
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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