Dimethylformamide dimethyl acetal → HCID 178484346, compound
Reaction equation
[C:1]([C:3]1[C:4]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=2[Cl:26])=[C:5]([C:16]([NH2:18])=[O:17])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH2:14][OH:15])[CH2:9]1)#[N:2].CO[CH:29](OC)[N:30]([CH3:32])[CH3:31]>>[C:1]([C:3]1[C:4]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=2[Cl:26])=[C:5]([C:16](/[N:18]=[CH:29]/[N:30]([CH3:32])[CH3:31])=[O:17])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH2:14][OH:15])[CH2:9]1)#[N:2]Participants
Procedure
A mixture of 4-cyano-3-(2,4-dichlorophenyl)-5-[2-(hydroxymethyl)morpholin-4-yl]thiophene-2-carboxamide (115 mg, 0.279 mmol) in 1,1-dimethoxy-N,N-dimethylmethanamine (3.44 mL, 0.025 mol) was flushed with argon and then irradiated in microwave at 160° C. for 60 min. The reaction mixture was concentrated to give 4-cyano-3-(2,4-dichlorophenyl)-N-[(1E)-(dimethylamino)methylene]-5-[2-(hydroxymethyl)morpholin-4-yl]thiophene-2-carboxamide (130 mg, 99%). LCMS: (FA) ES+ 467. To the above intermediate in AcOH (4.3 mL, 0.076 mol) was added hydrazine hydrate (100 mg, 0.003 mol). The mixture was flushed with argon and then irradiated in microwave at 120° C. for 20 min. The mixture was concentrated to remove the solvent. The residue was purified using ISCO chromatography on silica gel, elution 1:1 hexane-ethyl acetate to ethylacetate to afford 4-(2,4-dichlorophenyl)-2-[2-(hydroxymethyl)morpholin-4-yl]-5-(4H-1,2,4-triazol-3-yl)thiophene-3-carbonitrile (90 mg, 70%). LCMS: (FA) ES+ 436, 1H NMR (400 MHz, d4-methanol) δ: 8.28 (s, 1H), 7.55 (d, 1H), 7.41 (dd, 1H), 7.34 (d, 1H), 4.12-3.72 (m, 5H), 3.68-3.61 (m, 2H), 3.30-3.20 (m, 1H), 3.12-3.02 (m, 1H).
Workup
- customwas flushed with argon
- customirradiated in microwave at 160° C. for 60 min
- concentrationThe reaction mixture was concentrated
Sources & evidence
- ORD record
- ord-bc1093caefd54517a31295e96450cfd7
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08183240B2
Reaction notes
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