Lawesson's reagent → N5-(1-carbamothioylcyclopropyl)-6-chloro-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide

HRID 514271Notes

Reaction equation

HRID 514271 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:13]([NH:15][CH:16]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[C:17]([F:20])([F:19])[F:18])=[O:14])[N:8]2[CH2:11][CH3:12])=[CH:4][C:3]=1[C:31]([NH:33][C:34]1([C:37]#[N:38])[CH2:36][CH2:35]1)=[O:32].COC1C=CC(P2(=S)SP(=S)(C3C=CC(OC)=CC=3)[S:48]2)=CC=1>O1CCCC1.C(OCC)(=O)C>[C:37]([C:34]1([NH:33][C:31]([C:3]2[CH:4]=[C:5]3[C:9](=[CH:10][C:2]=2[Cl:1])[N:8]([CH2:11][CH3:12])[C:7]([C:13]([NH:15][CH:16]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:28])[F:29])[CH:22]=2)[C:17]([F:18])([F:20])[F:19])=[O:14])=[CH:6]3)=[O:32])[CH2:35][CH2:36]1)(=[S:48])[NH2:38]

Participants

5

Reactant 2

HCID 87949Lawesson's reagent2×HCID 601689226-chloro-N5-(1-cyanocyclopropyl)-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide

Product 1

HCID 86713989N5-(1-carbamothioylcyclopropyl)-6-chloro-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamideYield 12.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-Chloro-N5-(1-cyanocyclopropyl)-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide (0.200 g, 0.35 mmol) is initially charged in tetrahydrofuran (5.5 ml) under argon, 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulphide (0.305 g, 0.75 mmol) is added and the mixture is stirred at room temperature for 48 h. Then 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulphide (0.150 g, 0.38 mmol) is added again and the mixture is stirred at room temperature for a further 12 h. The reaction mixture is then diluted with ethyl acetate and washed with a sodium hydrogencarbonate solution. The organic phase is dried with magnesium sulphate, filtered and concentrated under reduced pressure. The residue is purified by means of preparative HPLC (Kromasil100, C18 250×20; eluent: acetonitrile in water, gradient: 10-100%) to obtain 0.025 g (11% of theory) of N5-(1-carbamothioylcyclopropyl)-6-chloro-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide.

Workup

  1. stirringthe mixture is stirred at room temperature for a further 12 h
  2. washwashed with a sodium hydrogencarbonate solution
  3. dry with materialThe organic phase is dried with magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by means of preparative HPLC (Kromasil100, C18 250×20

Sources & evidence

ORD record
ord-21eecabfeaaf4c66a95903c91b39de8a
Source dataset
uspto-grants-2015_08
Patent number
US09107411B2

Reaction notes

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