Methyl 5-methylthio-4-(2-naphthylamino)thiophene-2-carboxylate → 5-Methylthio-4-(2-naphthylamino)thiophene-2-carboxamidine
Reaction equation
Cl.[CH3:2][S:3][C:4]1[S:8][C:7]([C:9]([NH2:11])=[NH:10])=[CH:6][C:5]=1[NH:12][C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=1.CSC1SC(C(OC)=O)=CC=1NC1C=CC2C(=CC=CC=2)C=1.C[Al](C)C.[NH4+].[Cl-]>>[CH3:2][S:3][C:4]1[S:8][C:7]([C:9]([NH2:11])=[NH:10])=[CH:6][C:5]=1[NH:12][C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=1Participants
Procedure
5-Methylthio-4-(2-naphthylamino)thiophene-2-carboxamidine hydrochloride: Using a procedure similar to Example 154, step(b),730 mg (2.21 mmol) of methyl 5-methylthio-4-(2-naphthylamino)thiophene-2-carboxylate was allowed to react with 8 equiv (17.7 mmol) of the AlMe3/NH4Cl reagent and purified by preparative thin layer chromatography (20%-MeOH-CHCl3-sat'd. NH3, 1000 μm SiO2 plate) to afford 5-methylthio-4-(2-naphthylamino)thiophene-2-carboxamidine, which was dissolved in 4 mL of dry MeOH, cooled to 0° C. and carefully treated with 1.6 mL(1.5 equiv, 3.31 mmol) of 2M HCl in ether. The reaction was stored at 5° C. overnight, then concentrated in vacuo with toluene (3×10 mL) and then hexanes (2×10 mL). The yellow solid was dried under vacuum to afford 415 mg (53.6%) of 5-methylthio-4-(2-naphthylamino)thiophene-2-carboxamidine hydrochloride. 1H NMR (DMSO-d6, 400 MHz) δ 2.53 (s, 3H), 7.20 (d, 1H, J=2.2 Hz), 7.24-7.31 (m, 2H), 7.38 (m, 1H), 7.69 (d, 1H, 8.1 Hz), 7.75-7.79 (m, 2H), 8.13 (s, 1H), 8.24 (s, 1H), 9.06 (bs, 2H), 9.33 (bs, 2H). Mass spectrum (ESI, m/z): Calcd. for C16H15N3S2, 314.08 (M+H), found 314.5.
Workup
- custompurified by preparative thin layer chromatography (20%-MeOH-CHCl3-sat'd. NH3, 1000 μm SiO2 plate)
Sources & evidence
- ORD record
- ord-3b00b0be8063481086196f0d2475c567
- Source dataset
- uspto-grants-2001_09
- Patent number
- US06291514B1
Reaction notes
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