Dimethylformamide dimethyl acetal → HCID 58980884, compound

HRID 1181339Notes

Reaction equation

HRID 1181339 reaction equation
[NH2:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=2)[S:4][C:3]=1[C:14]([O:16]C)=O.[CH3:18]OC(OC)N(C)C.[CH2:26]([O:28][CH:29]([O:41][CH2:42][CH3:43])[CH2:30][O:31][C:32]1[CH:38]=[CH:37][C:35]([NH2:36])=[CH:34][C:33]=1[O:39][CH3:40])[CH3:27]>C(O)C>[Cl:13][C:10]1[CH:9]=[CH:8][C:7]([C:5]2[S:4][C:3]3[C:14](=[O:16])[N:36]([C:35]4[CH:37]=[CH:38][C:32]([O:31][CH2:30][CH:29]([O:28][CH2:26][CH3:27])[O:41][CH2:42][CH3:43])=[C:33]([O:39][CH3:40])[CH:34]=4)[CH:18]=[N:1][C:2]=3[CH:6]=2)=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 78373Dimethylformamide dimethyl acetalHCID 2777492Methyl 3-amino-5-(4-chlorophenyl)thiophene-2-carboxylateHCID 114367644-(2,2-Diethoxyethoxy)-3-methoxyaniline

Product 1

HCID 58980884HCID 58980884, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
90 °C

Procedure

To a solution of methyl 3-amino-5-(4-chlorophenyl)-2-thiophenecarboxylate (2.0 g, 7.47 mmol, Maybridge, Inc) in ethanol (20 mL) was added dimethylformamide dimethyl acetal (2.5 mL, 2.5 eq, Aldrich). The reaction mixture was refluxed in a 90° C. oil bath for 3 h at which point the solvents were removed by rotary evaporation. Coevaporation with toluene removed the excess dimethylformamide dimethyl acetal. To the resulting residue was added ethanol (20 mL) and 4-(2,2-diethoxyethoxy)-3-methoxyaniline (2.3 g, 1.2 eq, Example H1). The reaction mixture was heated to 100° C. for 36 hours. The solvent was removed by rotary evaporation and the product purified by column chromatography followed by recrystallization from hot MeOH yielding the intermediate (0.82 g, 22%). 1H NMR (CDCl3) δ 1.22 (6H, t), 3.63-3.83 (4H, m), 3.90 (3H, s), 4.14 (2H, d, J=5.3 Hz), 4.92 (1H, t, J=5.2 Hz), 6.97 (2H), 7.06 (1H, d, J=8.5 Hz), 7.46 (2H, d, J=8.5 Hz), 7.58 (1H, s), 7.68 (2H, d, J=8.4 Hz), 8.24 (1H, br, s). LCMS m/z=501 (m+H+).

Workup

  1. customwere removed by rotary evaporation
  2. customCoevaporation with toluene removed the excess dimethylformamide dimethyl acetal
  3. temperatureThe reaction mixture was heated to 100° C. for 36 hours
  4. customThe solvent was removed by rotary evaporation
  5. customthe product purified by column chromatography
  6. customfollowed by recrystallization from hot MeOH yielding the intermediate (0.82 g, 22%)

Sources & evidence

ORD record
ord-5973a2071c764f3f86cac406276b2574
Source dataset
uspto-grants-2007_10
Patent number
US07285557B2

Reaction notes

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