1-Hydroxybenzotriazole → 4-Anilino-5-chloro-2-{4-{N-[3-(imidazol-1-yl)propyl]carbamoyl}anilino}pyrimidine

4-Anilino-2-(4-carboxyanilino)-5-chloropyrimidine (Method 1; 170 mg, 0.5 mmol) was added to 1-(3-aminopropyl)imidazole (93.9 mg, 0.75 mmol) in a reaction tube. 1-Hydroxybenzotriazole (101 mg, 0.75 mmol) was added followed by N,N-diisopropylethylamine (130 mL 0.75 mmol) in DCM (4 ml). The mixture was flushed with argon and then stirred for 1 hour. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (105 mg, 0.55 mmol) in DCM (3 ml) was added and the mixture was stirred for 16 hours. The mixture was washed with saturated sodium bicarbonate solution (10 ml), water (10 ml) and saturated sodium chloride solution (10 ml), and the organic phase was loaded on a Varian Mega Bond Elut column. Elution with 0-10% 2.0M methanolic ammonia solution in DCM gave the product (11.6 mg, 5.2%). NMR: 2.0-2.15 (m, 2H), 3.0-3.1 (m, 2H), 4.25 (t, 2H), 7.25 (t, 1H), 7.4 (t, 2H), 7.6 (d, 4H), 7.7 (s, 1H), 7.75 (d, 2H), 7.85 (d, 1H), 8.3 (s, 1H), 8.6 (br t, 1H), 9.25 (d, 1H), 9.6 (br s, 1H), 10.3 (br s, 1H); LCMS (MH+): 448; HPLC (RT, System A): 6.16.

1. customThe mixture was flushed with argon
2. stirringthe mixture was stirred for 16 hours
3. washThe mixture was washed with saturated sodium bicarbonate solution (10 ml), water (10 ml) and saturated sodium chloride solution (10 ml)
4. washElution with 0-10% 2.0M methanolic ammonia solution in DCM

ORDレコード

ord-81b3dcd8767240a3875861bb63882bdc

出典データセット

uspto-grants-2003_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06649608B2