1,2-Dichloro-3-isocyanatobenzene → 1-(5-Tert-butyl-3-(2-ethyl-2-methyl-3-oxopiperazine-1-carbonyl)thiophen-2-yl)-3-(2,3-dichlorophenyl)urea

HRID 18920Notes

Reaction equation

HRID 18920 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:5][C:6]=1[C:7]([N:9]1[CH2:14][CH2:13][NH:12][C:11](=[O:15])[C:10]1([CH2:17][CH3:18])[CH3:16])=[O:8].[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([N:30]=[C:31]=[O:32])[C:25]=1[Cl:33]>C1COCC1>[C:19]([C:4]1[S:3][C:2]([NH:1][C:31]([NH:30][C:26]2[CH:27]=[CH:28][CH:29]=[C:24]([Cl:23])[C:25]=2[Cl:33])=[O:32])=[C:6]([C:7]([N:9]2[CH2:14][CH2:13][NH:12][C:11](=[O:15])[C:10]2([CH2:17][CH3:18])[CH3:16])=[O:8])[CH:5]=1)([CH3:21])([CH3:20])[CH3:22]

Participants

4

Reactant 2

HCID 330501,2-Dichloro-3-isocyanatobenzeneHCID 58679278HCID 58679278, compound

Product 1

HCID 586793261-(5-Tert-butyl-3-(2-ethyl-2-methyl-3-oxopiperazine-1-carbonyl)thiophen-2-yl)-3-(2,3-dichlorophenyl)ureaYield 44.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 4-(2-amino-5-tert-butylthiophene-3-carbonyl)-3-ethyl-3-methylpiperazin-2-one (72.0 mg, 0.22 mmol) in THF (2 mL) was added 1,2-dichloro-3-isocyanatobenzene (50.0 mg, 0.27 mmol). The resulting reaction mixture was stirred at room temperature and the reaction progress monitored by SFC-MS. When the reaction was completed, solvent was removed under reduced pressure and the crude product purified by preparative TLC to afford 1-(5-tert-butyl-3-(2-ethyl-2-methyl-3-oxopiperazine-1-carbonyl)thiophen-2-yl)-3-(2,3-dichlorophenyl)urea (50 mg, 44%) as pale yellow solid. 1H NMR (400 MHz, DMSO-d6): δ (ppm) 9.93 (s, 1H), 9.52 (s, 1H), 8.10 (s, 1H), 7.86 (d, J=8.2 Hz, 1H), 7.26-7.22 (m, 2H), 6.46 (s, 1H), 3.62-3.58 (m, 1H), 3.40-3.35 (m, 1H), 3.30-3.23 (m, 1H), 3.19-3.13 (m, 1H), 2.65-2.61 (m, 1H), 1.89-1.85 (m, 1H), 1.58 (s, 3H), 1.22 (s, 9H), 0.69 (t, J=7.4 Hz, 3H).

Workup

  1. customThe resulting reaction mixture
  2. customsolvent was removed under reduced pressure
  3. customthe crude product purified by preparative TLC

Sources & evidence

ORD record
ord-d48686ac2ea74bda8f3f416086f00a52
Source dataset
uspto-grants-2010_06
Patent number
US07741479B2

Reaction notes

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