Hydrochloric Acid → 5-(3,3-Dimethyl-but-1-ynyl)-3-{(4-methyl-cyclohexanecarbonyl)-[4-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-cyclohexyl]-amino}-thiophene-2-carboxylic acid

HRID 1046426Notes

Reaction equation

HRID 1046426 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:33]#[C:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[CH:8][C:9]=1[N:10]([C:24]([CH:26]1[CH2:31][CH2:30][CH:29]([CH3:32])[CH2:28][CH2:27]1)=[O:25])[CH:11]1[CH2:16][CH2:15][CH:14]([S:17][C:18]2[N:22]([CH3:23])[CH:21]=[N:20][N:19]=2)[CH2:13][CH2:12]1)=[O:4].[Li+].[OH-].Cl>C1COCC1.O>[CH3:36][C:35]([CH3:37])([CH3:38])[C:34]#[C:33][C:7]1[S:6][C:5]([C:3]([OH:4])=[O:2])=[C:9]([N:10]([C:24]([CH:26]2[CH2:27][CH2:28][CH:29]([CH3:32])[CH2:30][CH2:31]2)=[O:25])[CH:11]2[CH2:12][CH2:13][CH:14]([S:17][C:18]3[N:22]([CH3:23])[CH:21]=[N:20][N:19]=3)[CH2:15][CH2:16]2)[CH:8]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 581140735-(3,3-Dimethyl-but-1-ynyl)-3-{(4-methyl-cyclohexanecarbonyl)-[4-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-cyclohexyl]-amino}-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 581139105-(3,3-Dimethyl-but-1-ynyl)-3-{(4-methyl-cyclohexanecarbonyl)-[4-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-cyclohexyl]-amino}-thiophene-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-(3,3-Dimethyl-but-1-ynyl)-3-{(4-methyl-cyclohexanecarbonyl)-[4-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-cyclohexyl]-amino}-thiophene-2-carboxylic acid methyl ester (63 mg, 0.113 eq.) was dissolved in THF (2.0 mL) in a round-bottomed flask. A solution of LiOH (14 mg, 0.34 mmol, 3.0 eq.) in water (1.0 mL) was added. The reaction was stirred at room temperature overnight. The reaction was then neutralized with 0.2 mL 2 N HCl, concentrated, and purified by reverse phase preparative HPLC to afford Example 2 (5-(3,3-dimethyl-but-1-ynyl)-3-{(4-methyl-cyclohexanecarbonyl)-[4-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-cyclohexyl]-amino}-thiophene-2-carboxylic acid, 27 mg, 44%).

Workup

  1. concentrationconcentrated
  2. custompurified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-e7f6a6fcb489455fb55c855c38d750c4
Source dataset
uspto-grants-2013_10
Patent number
US08569302B2

Reaction notes

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