4-Pyridinemethanamine → (S)-Methyl 2-(4-chloro-8-oxo-9-(pyridin-4-ylmethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetate

(S)-Dimethyl 2-((7-chloro-4-(chloromethyl)-1H-indazol-5-yl)methyl)succinate (120 mg, 0.33 mmol) was dissolved in DMF (1.0 mL). 4-Aminomethylpyridine (100 μL, 1.0 mmol) was added to the mixture. Reaction stirred at room temperature for 24 hours. Mixture was diluted with ethyl acetate. Mixture was washed twice with water and once with brine. Organic was dried (magnesium sulfate), filtered and concentrated in vacuo. Residue was dissolved in toluene (4 mL). Acetic acid (1 mL) was added to the mixture. Reaction was heated at reflux for 3.5 hours. Mixture was cooled to room temperature then diluted with ethyl acetate. Material was washed once with water and twice with aqueous sodium bicarbonate. Aqueous was made basic with sodium bicarbonate. Back extracted from the aqueous twice with ethyl acetate. Combined organics were dried (magnesium sulfate), filtered and concentrated in vacuo. Residue was purified with silica gel chromatography eluting dichloromethane and 2N ammonia in methanol. Title compound was obtained as yellow solid in 48% yield.

1. customReaction
2. washMixture was washed twice with water and once with brine
3. dry with materialOrganic was dried (magnesium sulfate)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. dissolutionResidue was dissolved in toluene (4 mL)
7. additionAcetic acid (1 mL) was added to the mixture
8. customReaction
9. temperaturewas heated
10. temperatureat reflux for 3.5 hours
11. temperatureMixture was cooled to room temperature
12. washMaterial was washed once with water and twice with aqueous sodium bicarbonate
13. extractionBack extracted from the aqueous twice with ethyl acetate
14. dry with materialCombined organics were dried (magnesium sulfate)
15. filtrationfiltered
16. concentrationconcentrated in vacuo
17. customResidue was purified with silica gel chromatography
18. washeluting dichloromethane and 2N ammonia in methanol

ORDレコード

ord-3ed04bff3d1249cf82994da609133364

出典データセット

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07384930B2