Ethanethiol → 4-Chloro-1-[4-hydroxy-2-((S)-3-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)-phenyl]-5-methyl-1H-pyrazole-3-carboxylic acid dibutylamide

HRID 2274581Notes

Reaction equation

HRID 2274581 reaction equation
[CH2:1]([N:5]([CH2:37][CH2:38][CH2:39][CH3:40])[C:6]([C:8]1[C:12]([Cl:13])=[C:11]([CH3:14])[N:10]([C:15]2[CH:20]=[CH:19][C:18]([O:21]C)=[CH:17][C:16]=2[C:23]([N:25]2[C@H:34]([CH2:35][OH:36])[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:26]2)=[O:24])[N:9]=1)=[O:7])[CH2:2][CH2:3][CH3:4].[Cl-].[Al+3].[Cl-].[Cl-].C(S)C.ClCCl>O>[CH2:37]([N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[C:6]([C:8]1[C:12]([Cl:13])=[C:11]([CH3:14])[N:10]([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][C:16]=2[C:23]([N:25]2[C@H:34]([CH2:35][OH:36])[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:26]2)=[O:24])[N:9]=1)=[O:7])[CH2:38][CH2:39][CH3:40]

Participants

6

Reactant 4

HCID 6343EthanethiolHCID 6344DichloromethaneHCID 6451240Aluminum(III) ChlorideHCID 716177154-Chloro-1-[2-((S)-3-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)-4-methoxy-phenyl]-5-methyl-1H-pyrazole-3-carboxylic acid dibutylamide

Product 1

HCID 716174794-Chloro-1-[4-hydroxy-2-((S)-3-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)-phenyl]-5-methyl-1H-pyrazole-3-carboxylic acid dibutylamideYield 33%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 4-chloro-1-[2-((S)-3-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)-4-methoxy-phenyl]-5-methyl-1H-pyrazole-3-carboxylic acid dibutylamide (40 mg, 0.071 mmol) and aluminium chloride (75 mg, 0.56 mmol) was stirred in ethanethiol (0.052 mL, 0.71 mmol) and dichloromethane (0.5 mL) for 12 hours at ambient temperature under a nitrogen atmosphere. The mixture was added with water and extracted with 1:4 methanol:methylene chloride. The organic layer was removed in vacuo. After eluting through a short pad of silica gel column and C18 column, the crude material was purified by HPLC to afford the title compound (9 mg, 33% yield). MS (ESI) [m/e, (M+H)+]=553.5. 1H NMR (400 MHz, DMSO-d6) δ ppm 6.66-7.50 (m, 7H), 2.03-5.08 (m, 14H), 0.53-1.62 (m, 14H).

Workup

  1. extractionextracted with 1:4 methanol
  2. customThe organic layer was removed in vacuo
  3. washAfter eluting through a short pad of silica gel column and C18 column
  4. customthe crude material was purified by HPLC

Sources & evidence

ORD record
ord-5f2432dcd1e44561bbf03931db11b748
Source dataset
uspto-grants-2015_09
Patent number
US09126980B2

Reaction notes

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