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Triethylamine → 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

HRID 1046425
Notes
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Reaction equation

HRID 1046425 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:27]#[C:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:8][C:9]=1[N:10]([CH:20]1[CH2:25][CH2:24][CH:23](O)[CH2:22][CH2:21]1)[C:11]([CH:13]1[CH2:18][CH2:17][CH:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4].[CH3:33][N:34]1[CH:38]=[N:37][N:36]=[C:35]1[SH:39].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.C(N(CC)CC)C>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:27]#[C:28][C:29]([CH3:30])([CH3:32])[CH3:31])=[CH:8][C:9]=1[N:10]([C:11]([CH:13]1[CH2:18][CH2:17][CH:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])[CH:20]1[CH2:25][CH2:24][CH:23]([S:39][C:35]2[N:34]([CH3:33])[CH:38]=[N:37][N:36]=2)[CH2:22][CH2:21]1)=[O:4]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 581139915-(3,3-Dimethyl-but-1-ynyl)-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl esterHCID 178481306HCID 178481306, compound

Product 1

HCID 58114073
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
Yield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5-(3,3-Dimethyl-but-1-ynyl)-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (92 mg, 0.2 mmol, 1.0 eq.), 4-methyl-4H-[1,2,4]triazole-3-thiol (46 mg, 0.4 mmol, 2.0 eq.), triphenylphosphine (105 mg, 0.4 mmol, 2.0 eq.), DIAD (77 μL, 0.4 mmol, 2.0 eq.) and triethyl amine (42 μL, 0.3 mmol, 1.5 eq.) were weighed into a round-bottomed flask containing THF (2.0 mL). The solution was purged with N2 and stirred at room temperature for 12 h. The solution was concentrated to an oil and then purified by silica gel chromatography (0-100% EtOAc in hexanes) to afford 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, 57%).

Workup

  1. customThe solution was purged with N2
  2. concentrationThe solution was concentrated to an oil
  3. custompurified by silica gel chromatography (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-432ca556faaf40518cdbb7f9dc7e0075
Source dataset
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08569302B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes