N-(2-FURYLMETHYL)-N-(THIEN-2-YLMETHYL)AMINE synthesis

Yield:90921-60-1 86%

Reaction Conditions:

Stage #1: thiophene-2-carbaldehyde;furan-2-ylmethanamine in ethanol at 120; for 0.5 h;Microwave irradiation;
Stage #2: with sodium tetrahydroborate;ethanol at 23 - 90; for 19 h;

Steps:

3 1-(furan-2-yl)-N-(thiophen-2-ylmethyl)methanamine

1-(furan-2-yl)-N-(thiophen-2-ylmethyl)methanamine
A mixture containing furan-2-ylmethanamine (1.00 mL, 11.32 mmol) and thiophene-2-carbaldehyde (1.06 mL, 11.32 mmol) in EtOH (22.6 mL) was heated in themicrowave reactor at 120 °C for 0.5 h.
The reaction solution was transferred to a round-bottomed flask, and was then treated with sodium borohydride (0.856 g, 22.63 mmol) at 90 °C for 3 h, then at 23 °C for 16 h. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned between 50 mL of dichloromethane (DCM) and 50 mL of water. The product was extracted with two 25-mL portions of DCM and the combined organic layer was washed with 50 mL of brine, and subsequently dried over anhydrous sodium sulfate (Na₂S0₄). The dried organic layer was concentrated under reduced pressure and purified by silica gel column chromatography(100 g); gradient elution from 90: 10 to 50:50 Hex:EtOAc afforded l-(furan- 2-yl)-N-(thiophen-2-ylmethyl)methanamine (1) as a clear light pale yellow oil; yield: 1.87 g (86 %). LC-MS: t = 1.77 min. 1H NMR (400 MHz, CDCI3) δ 7.38 (dd, J = 1.9, 0.8 Hz, 1H),7.22 (dd, J = 4.8, 1.4 Hz, 1H), 6.98 - 6.92 (m, 2H), 6.32 (dd, J = 3.2, 1.9 Hz, 1H), 6.22 - 6.18 (m, 1H), 3.99 (d, J = 0.7 Hz, 2H), 3.82 (s, 2H), 1.98 (s, 2H). ¹³C NMR (101 MHz, CDC1₃) δ 153.5, 143.5, 142.1, 126.8, 125.4, 124.7, 110.3, 107.5, 47.2, 45.0.HRMS (ESI) m/z 194.0635 (M + H)⁺ (C₁₀Hi₂NOS requires 194.0634).

References:

WO2016/4180,2016,A1 Location in patent:Paragraph 00212; 00213; 00214