Hydrochloric Acid → HCID 89781229, compound

Participants

Reaction Conditions

Reaction Steps

A 50-mL round-bottom flask was charged with 30.1 (130 mg, 0.28 mmol, 1.00 equiv) and dichloromethane (10 mL) and cooled to 0° C. Then hydrochloric acid (12 M, 2.0 mL) was added and the resulting solution was stirred for 3 h at room temperature. After 3 h, the mixture was concentrated under vacuum. The pH value of the solution was adjusted to 8 with saturated aqueous sodium carbonate and then the solution was extracted with 2×40 mL of ethyl acetate. The organic layers were combined and dried over sodium sulfate and concentrated under vacuum to give 1-[(3R)-12-[(4-aminocyclohexyl)amino]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]butan-2-ol (80 mg, crude) as a colorless oil. To a solution of this material (80 mg, crude) in methanol (5 mL) was added HCHO (37%, 0.8 mL). The reaction was stirred for 1 h at room temperature. Then NaBH3CN (33.9 mg, 0.54 mmol, 2.44 equiv) was added and the resulting solution was stirred for an additional 2 h at ambient temperature and concentrated under vacuum. The crude product (80 mg) was purified by preparative HPLC(SHIMADZU) under the following conditions: column: SunFire Prep C18, 19*150 mm 5 um; mobile phase: water with 0.1% HCOOH and CH3CN; UV detection at 254 nm. The product-containing fractions were collected and evaporated to remove the water and CH3CN to give (2R)-1-[(3R)-12-[[4-(dimethylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]butan-2-ol formate (I-52, 8.6 mg) as a white solid and (2S)-1-[(3R)-12-[[4-(dimethylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]butan-2-ol formate (I-54, 5.9 mg) as a grey solid, respectively.

Provenance & Evidence