Dimethylformamide dimethyl acetal → 4-cyano-3-(2,4-dichlorophenyl)-N-((dimethylamino)methylene)-5-morpholinothiophene-2-carboxamide

HRID 2091673Notes

Reaction equation

HRID 2091673 reaction equation
[C:1]([C:3]1[C:4]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[Cl:24])=[C:5]([C:14]([NH2:16])=[O:15])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2].CO[CH:27](OC)[N:28]([CH3:30])[CH3:29]>>[C:1]([C:3]1[C:4]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[Cl:24])=[C:5]([C:14]([N:16]=[CH:27][N:28]([CH3:30])[CH3:29])=[O:15])[S:6][C:7]=1[N:8]1[CH2:9][CH2:10][O:11][CH2:12][CH2:13]1)#[N:2]

Participants

3

Reactant 2

HCID 78373Dimethylformamide dimethyl acetalHCID 441554464-Cyano-3-(2,4-dichlorophenyl)-5-morpholinothiophene-2-carboxamide

Product 1

HCID 670726914-cyano-3-(2,4-dichlorophenyl)-N-((dimethylamino)methylene)-5-morpholinothiophene-2-carboxamide

Procedure

A mixture of 4-cyano-3-(2,4-dichlorophenyl)-5-morpholin-4-ylthiophene-2-carboxamide (31.6 mg, 0.0000827 mol) in 1,1-dimethoxy-N,N-dimethylmethanamine (1.0 mL, 0.0075 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-((dimethylamino)methylene)-5-morpholinothiophene-2-carboxamide as intermediate (31 mg, 86%). LCMS: (FA) ES+ 437.13. 1H NMR (400 MHz, d6-DMSO) δ: 8.34 (s, 1H), 7.69 (d, 1H), 7.47 (d, 1H), 7.33 (d, 1H), 3.79-3.74 (m, 4H), 3.59-3.54 (m, 4H), 3.07 (s, 3H), 2.72 (s, 3H). To the above intermediate in AcOH (1.8 mL, 0.032 mol) was added hydrazine hydrate (50 mg, 0.001 mol). The mixture was flushed with argon and then irradiated in microwave at 120° C. for 20 min. The mixture was concentrated to remove most of the solvent. Water was added to the residue and the precipitate was collected, washed with water, dried to afford 4-(2,4-dichlorophenyl)-2-morpholino-5-(4H-1,2,4-triazol-3-yl)thiophene-3-carbonitrile (12.8 mg, 55%). LCMS: (FA) ES+ 406.11, ES− 404.21, 1H NMR (400 MHz, d6-DMSO) δ: 14.00 (s, 1H), 8.43 (s, 1H), 7.74 (d, 1H), 7.49 (d, 1H), 7.41 (d, 1H), 3.82-3.76 (m, 4H), 3.56-3.51 (m, 4H).

Workup

  1. customwas flushed with argon
  2. customirradiated in microwave at 160° C. for 60 min
  3. concentrationThe reaction mixture was concentrated

Sources & evidence

ORD record
ord-297b72d657d94a4cade8a5b8c92eaee3
Source dataset
uspto-grants-2013_05
Patent number
US08440664B2

Reaction notes

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