Triethylsilane → Methyl 3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxylate

HRID 1171888Notes

Reaction equation

HRID 1171888 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][CH:7]=[CH:8][C:9]=1[NH2:10])=[O:4].[N:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([CH:21]=O)=[CH:13][CH:12]=1.C([SiH](CC)CC)C.[OH-].[Na+].C([O-])(O)=O.[Na+]>C(O)(C(F)(F)F)=O.C(Cl)Cl.C(Cl)Cl>[N:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([CH2:21][NH:10][C:9]2[CH:8]=[CH:7][S:6][C:5]=2[C:3]([O:2][CH3:1])=[O:4])=[CH:13][CH:12]=1

Participants

8

Reactant 5

HCID 12052TriethylsilaneHCID 14798Sodium HydroxideHCID 780724-QuinolinecarboxaldehydeHCID 89652Methyl 3-amino-2-thiophenecarboxylateHCID 516892Sodium Bicarbonate

Product 1

HCID 59734303Methyl 3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 3-amino-thiophene-2-carboxylic acid methyl ester (5 g, 31.8 mmol) and 4-quinoline-carboxaldehyde (5.25 g, 33.4 mmol) in TFA/CH2Cl2 (75 mL, 75 mL) was heated at 50° C. for 3.5 h. The solution was cooled in an ice bath and triethylsilane (10.2 mL, 63.6 mmol) was added drop-wise over 5 min. The reaction mixture was stirred at 50° C. for 3.5 h, cooled to rt, and 500 mL of CH2Cl2 was added. The reaction mixture was basified with 10N NaOH (pH 6-7) followed by sat. NaHCO3 (pH 8). The CH2Cl2 layer was separated and the aqueous layer was extracted with CH2Cl2 (2×100 mL). The organic extracts were combined, washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to yield the crude product, which was triturated with hexane to give pure methyl 3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxylate as white solid. MS (ES): m/z 298.55 (100) [MH+]; 1H-NMR (400 MHz/CDCl3): δ3.87 (s, 3H), 5.00 (d, J=4.0 Hz, 2H), 6.48 (d, J=5.6 Hz, 1H), 7.30 (d, J=5.6 Hz, 1H), 7.36 (m, 1H), 7.41 (d, J=4.4 Hz, 1H), 7.62 (t, J=8.0 Hz, 1H), 7.76 (t, J=9.6 Hz, 1H), 8.01 (d, J=8.0 Hz, 1H), 8.17 (d, J=8.4 Hz, 1H), 8.86 (d, J=4.4 Hz, 1H).

Workup

  1. temperatureThe solution was cooled in an ice bath
  2. temperaturecooled to rt
  3. customThe CH2Cl2 layer was separated
  4. extractionthe aqueous layer was extracted with CH2Cl2 (2×100 mL)
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto yield the crude product, which
  10. customwas triturated with hexane

Sources & evidence

ORD record
ord-176412a07b3b4e2996b448d9e0ce04f0
Source dataset
uspto-grants-2010_11
Patent number
US07829717B2

Reaction notes

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