4-{[4-Hydroxy-4-(trifluoromethyl)(1,3-thiazolin-2-yl)]amino}-5-methylthiothiophene-2-carboxamidine → 4-{[4-Hydroxy-4-(trifluoromethyl)(1,3-thiazolin-2-yl)]amino}-5-methylthiothiophene-2-carboxamidine

HRID 412977Notes

Reaction equation

HRID 412977 reaction equation
[OH:1][C:2]1([C:18]([F:21])([F:20])[F:19])[CH2:6][S:5][C:4]([NH:7][C:8]2[CH:9]=[C:10]([C:15]([NH2:17])=[NH:16])[S:11][C:12]=2[S:13][CH3:14])=[N:3]1.OC1(C(F)(F)F)CSC(NC2C=C(C(OC)=S)SC=2C)=N1.C[Al](C)C.[NH4+].[Cl-]>>[NH3:3].[OH:1][C:2]1([C:18]([F:20])([F:21])[F:19])[CH2:6][S:5][C:4]([NH:7][C:8]2[CH:9]=[C:10]([C:15]([NH2:17])=[NH:16])[S:11][C:12]=2[S:13][CH3:14])=[N:3]1

Participants

5

Reactant 3

HCID 185371554-{[4-Hydroxy-4-(trifluoromethyl)(1,3-thiazolin-2-yl)]amino}-5-methylthiothiophene-2-carboxamidineHCID 22243074Ammonium chloride trimethylaluminiumHCID 131723714Methyl 4-{[4-hydroxy-4-(trifluoromethyl)(1,3-thiazolin-2-yl)]amino}-5-methylthiothiophene-2-carboxylate

Product 2

HCID 222AmmoniaHCID 185371554-{[4-Hydroxy-4-(trifluoromethyl)(1,3-thiazolin-2-yl)]amino}-5-methylthiothiophene-2-carboxamidineYield 28%

Procedure

4-{[4-Hydroxy-4-(trifluoromethyl)(1,3-thiazolin-2-yl)]amino}-5-methylthiothiophene-2-carboxamidine: Using a procedure similar to Example 154, step (b), 40 mg (0.11 mmol) of methyl 4-{[4-hydroxy-4-(trifluoromethyl)(1,3-thiazolin-2-yl)]amino}-5-methylthiothiophene-2-carboxylate was allowed to react with 8 equiv (0.89 mmol) of the AlMe3/NH4Cl reagent and purified by preparative thin layer chromatography 20%-MeOH—CHCl3-sat'd. NH3, 500 μm SiO2 plate) to afford 11 mg (28%) of 4-{[4-hydroxy-4-(trifluoromethyl)(1,3-thiazolin-2-yl)]amino}-5-methylthiothiophene-2-carboxamidine as a ca. 1:1 mixture of cyclized aminal and open imine tautomers. 1H NMR (DMSO-d6, 300 MHz) δ 2.73 (s, 3H tautomer), 2.89 (s, 3H tautomer), 3.36 (d, 2H, J=6.5 Hz), 3.62 (d, 2H, J=7.2 Hz), 7.95 (s, 1H), 8.36 (bs, 2H), 9.79 (bs, 1H). Mass spectrum (ESI, m/z): Calcd. for C10H11F3N4OS3, 357.01 (M+H), found 357.2.

Workup

  1. custompurified by preparative thin layer chromatography 20%-MeOH—CHCl3-sat'd

Sources & evidence

ORD record
ord-f7e6746a26e0463191f9783c93880904
Source dataset
uspto-grants-2003_05
Patent number
US06562840B1

Reaction notes

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