N-Acetyl-L-Cysteine → HCID 66817159, compound

HRID 1755081Notes

Reaction equation

HRID 1755081 reaction equation
[OH:1][C:2]1([CH3:35])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[CH:15]=[C:14]([CH3:16])[C:13](/[CH:17]=[CH:18]/[S:19]([N:22]3[CH2:33][CH2:32][C:25]4([NH:29][C:28](=S)[NH:27][C:26]4=[O:31])[CH2:24][CH2:23]3)(=[O:21])=[O:20])=[C:12]([CH3:34])[CH:11]=2)=[O:9])[CH2:4][CH2:3]1.[Cl:36][C:37]1[CH:38]=[C:39](B(O)O)[CH:40]=[CH:41][C:42]=1[Cl:43].C(N[C@H](C(O)=O)CS)(=O)C>CN1C(=O)CCC1.C1C=C(C([O-])=O)SC=1.[Cu+]>[Cl:36][C:37]1[CH:38]=[C:39]([C:28]2[NH:27][C:26](=[O:31])[C:25]3([CH2:32][CH2:33][N:22]([S:19](/[CH:18]=[CH:17]/[C:13]4[C:14]([CH3:16])=[CH:15][C:10]([C:8]([N:5]5[CH2:4][CH2:3][C:2]([OH:1])([CH3:35])[CH2:7][CH2:6]5)=[O:9])=[CH:11][C:12]=4[CH3:34])(=[O:20])=[O:21])[CH2:23][CH2:24]3)[N:29]=2)[CH:40]=[CH:41][C:42]=1[Cl:43]

Participants

6

Reactant 3

HCID 12035N-Acetyl-L-CysteineHCID 27343303,4-Dichlorobenzeneboronic acidHCID 86672789HCID 86672789, compound

Product 1

HCID 66817159HCID 66817159, compoundYield 44.1%

Reagents, catalysts & solvents 2

HCID 11194830Cuprous 2-thiophenecarboxylateCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 8-{(E)-2-[4-(4-hydroxy-4-methyl-piperidine-1-carbonyl)-2,6-dimethyl-phenyl]-ethenesulfonyl}-2-thioxo-1,3,8-triaza-spiro[4.5]decan-4-one (25 mg, 0.048 mmol), 3,4-dichlorophenylboronic acid (27.5 mg, 0.144 mmol), palladium tetrakistriphenylphosphine (11.1 mg, 0.0096 mmol) and CuTC (36.8 mg, 0.192 mmol) in NMP (0.1 mL) was heated with stirring at 80° C. for 30 minutes in a nitrogen atmosphere. After cooling to room temperature, N-acetylcysteine (33 mg, 0.2 mmol) was added to the reaction mixture. The reaction mixture was purified by silica gel column chromatography (NH silica gel, methylene chloride:methanol=100:0→90:10) to give 2-(3,4-dichloro-phenyl)-8-{(E)-2-[4-(4-hydroxy-4-methyl-piperidine-1-carbonyl)-2,6-dimethyl-phenyl]-ethenesulfonyl}-1,3,8-triaza-spiro[4.5]dec-1-en-4-one as a white solid (13.4 mg, 44%).

Workup

  1. temperatureAfter cooling to room temperature
  2. customThe reaction mixture was purified by silica gel column chromatography (NH silica gel, methylene chloride:methanol=100:0→90:10)

Sources & evidence

ORD record
ord-9e43f16d5f4f425c978fcca21d5bae92
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

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