Borohydride → HCID 178521638、化合物

To an emulsion of trans-3-aminocyclobutanol hydrochloride (287 mg, 2.322 mmol) in DCM (5 mL) was added methanol (20 mL), imidazo[1,2-a]pyridine-8-carbaldehyde (340 mg, 2.326 mmol) and diisopropylethylamine (0.446 mL, 2.55 mmol) and the reaction mixture was stirred at room temperature under nitrogen for 10 min. Sodium triacetoxyborohydride (1000 mg, 4.72 mmol) was then added and the reaction mixture was stirred under nitrogen for 2 hours when LCMS indicated the reaction to be complete. The reaction mixture was then concentrated in vacuo and the residue was taken up in DCM (200 mL) and aqueous 2M sodium hydroxide (200 mL) was added and the mixture was stirred at room temperature for 1 hour. The organic layer was separated, washed with water (2×200 mL) and the aqueous phase was back extracted using 3:1 chloroform:isopropanol (2×250 mL). The combined organic layers were dried using a hydrophobic frit and the solvent evaporated in vacuo. The residue was pre-absorbed on florosil and purified on a silica cartridge (100 g) using a 0-25% methanol-dichloromethane gradient over 60 min. The appropriate fractions were combined and evaporated in vacuo to give crude product still containing some borohydride residues. This material was dissolved in aqueous 2M sodium hydroxide (100 mL) and left at room temperature for 5 hours when sodium hydroxide pellets (ca. 0.5 g) was added and the mixture left at room temperature for a further 15 hours. The mixture was then extracted with 3:1 chloroform:isopropanol (2×300 mL) and the organic layer was separated, dried using a hydrophobic frit and the solvent evaporated in vacuo. The residue was dried on a high vacuum line for 2 hours to give the title compound as an orange oil (305 mg).

1. stirringthe reaction mixture was stirred under nitrogen for 2 hours when LCMS
2. customthe reaction
3. concentrationThe reaction mixture was then concentrated in vacuo
4. additionaqueous 2M sodium hydroxide (200 mL) was added
5. stirringthe mixture was stirred at room temperature for 1 hour
6. customThe organic layer was separated
7. washwashed with water (2×200 mL)
8. extractionthe aqueous phase was back extracted
9. customThe combined organic layers were dried
10. customthe solvent evaporated in vacuo
11. customThe residue was pre-absorbed on florosil
12. custompurified on a silica cartridge (100 g)
13. customover 60 min
14. customevaporated in vacuo
15. customto give crude product
16. additionwas added
17. waitthe mixture left at room temperature for a further 15 hours
18. extractionThe mixture was then extracted with 3:1 chloroform
19. customisopropanol (2×300 mL) and the organic layer was separated
20. customdried
21. customthe solvent evaporated in vacuo
22. customThe residue was dried on a high vacuum line for 2 hours

ORDレコード

ord-942e76a864cf4201901f1d074e916e1c

出典データセット

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08754101B2