تفاعل #328378

معادلة التفاعل

methyl [6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazol-2-yl]carbamate

hydrochloric acid

→

6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazol-2-amine

المردود 54.9%

المذيبات

methanol

potassium hydroxide

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe reaction mixture was cooled
2. 2
   تركيزconcentrated
3. 3
   workup.ADDITIONdiluted with ethyl acetate (10 mL)
4. 4
   غسيلwashed with brine solution (5 mL)
5. 5
   تجفيفdried over sodium sulfate
6. 6
   ترشيحfiltered
7. 7
   تركيزconcentrated
8. 8
   أخرىThe residue was purified by preparative reverse phase HPLC

الإجراء التجريبي

A mixture of methyl [6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazol-2-yl]carbamate (example 2) (60 mg, 0.11 mmol) in methanol and 2M potassium hydroxide (1:1, 2 mL) was stirred at 65° C. for 18 hours. The reaction mixture was cooled, adjusted to pH 10 with 2M hydrochloric acid, concentrated, diluted with ethyl acetate (10 mL), washed with brine solution (5 mL), dried over sodium sulfate, filtered, concentrated. The residue was purified by preparative reverse phase HPLC to give 6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazol-2-amine (29 mg, 54% yield). 1H NMR (400 MHz, Methanol-d4): 8.44 (1H), 7.37 (dd, 1H), 7.31 (s, 1H), 7.29 (s, 1H), 7.14 (dd, 1H), 7.07-7.01 (m, 2H), 6.99 to 6.91 (m, 3H), 6.70 (br, 1H), 4.49 (s, 2H), 4.26 (m, 2H), 3.95 (s, 2H), 3.86 (m, 2H), 2.19 (s, 3H), MS (EI) for C28H25FN6O: 481 (MH+).

المصدر