Formaldehyde → HCID 86695205, compound

Participants

Reaction Steps

To a solution of 2-[(3R)-12-[(4-amino-4-methylcyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetamide (200 mg, 0.55 mmol, 1.00 equiv) in 8 mL of methanol was added HCHO (37%, 1.2 mL). The solution was stirred for 0.5 h at room temperature. Then NaBH3CN (105 mg, 1.67 mmol, 3.01 equiv) was added and the resulting solution was allowed to react, with stirring, for an additional 1 h at room temperature. The reaction was quenched with NH4Cl (aq.) and extracted with 3×60 mL of DCM. The combined organic layers were concentrated under vacuum. The crude product (150 mg) was purified by preparative HPLC under the following conditions (Waters): column: XBridge Prep C18 OBD column: 5 um, 19*150 mm; mobile phase: water with 0.05% NH4HCO3 and CH3CN (5% CH3CN up to 47% in 13 min, up to 95% in 2 min, down to 5% in 2 min); flow rate: 20 mL/min; UV detection at 254 & 220 nm. This resulted in 39.8 mg of 2-[(3R)-12-[[4-(dimethylamino)-4-methylcyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetamide as a white solid. MS: m/z 389 (M+H)+. 1H NMR (300 MHz, CD3OD): δ 8.49 (1H, s), 5.41 (1H, m), 3.80 (1H, m), 3.19 (1H, m), 3.04 (1H, m), 2.98 (1H, m), 2.85 (6H, s), 2.76 (1H, m), 2.31 (4H, m), 2.14 (2H, m), 1.96 (4H, m), 1.47 (3H, s).

Provenance & Evidence