تفاعل #649496

معادلة التفاعل

NaBH(OAc)3

NaCNBH3

Allylamine

HOAc

3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(5-formyl-3-thienyl)-1H-indole-7-carboxamide

formaldehyde

→

title compound

المردود 23.1%

3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(5-{[methyl(2-propen-1-yl)amino]methyl}-3-thienyl)-1H-indole-7-carboxamide

المردود 23.1%

المذيبات

MeOH

DMSO

ظروف التفاعل

المعالجة

1. 1
   أخرىthe vial was capped
2. 2
   workup.STIRRINGthe reaction was stirred for an additional 4 h
3. 3
   workup.STIRRINGthe reaction was stirred for an additional 1 h
4. 4
   ترشيحThe reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 mL MeOH)
5. 5
   غسيلeluting in sequence with MeOH (3 mL)
6. 6
   تركيزThe NH3/MeOH fraction was concentrated under a stream of nitrogen at 50° C.
7. 7
   workup.DISSOLUTIONthe residue was dissolved in DMSO (1 mL)
8. 8
   أخرىpurified on a Gilson HPLC (Xbridge Prep C18 column: 19×100 mm)
9. 9
   غسيلeluting at 20 mL per min with a linear gradient
10. 10
    workup.WAITrunning from 10% CH3CN/H2O (0.1% NH4OH) to 70% CH3CN/H2O (0.1% NH4OH) over 15 min
11. 11
    workup.ADDITIONThe fractions containing the title compound
12. 12
    تركيزwere concentrated under a stream of nitrogen at 50° C.

الإجراء التجريبي

Allylamine (0.034 mL, 0.449 mmol) and HOAc (0.026 mL, 0.449 mmol) were added to a solution of 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(5-formyl-3-thienyl)-1H-indole-7-carboxamide (20 mg, 0.0449 mmol) in DMSO (0.5 mL) in a 1-dram vial. NaBH(OAc)3 (95 mg, 0.449 mmol) was then added, the vial was capped and the reaction was stirred at room temperature for 15 h. NaCNBH3 (28 mg, 0.449 mmol) and MeOH were added, and the reaction was stirred for an additional 4 h. An aqueous solution of 37 wt % formaldehyde (0.069 mL, 0.898 mmol) was added, and the reaction was stirred for an additional 1 h. The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 mL MeOH), eluting in sequence with MeOH (3 mL) and a 2 M solution of NH3/MeOH (9 mL). The NH3/MeOH fraction was concentrated under a stream of nitrogen at 50° C., and the residue was dissolved in DMSO (1 mL) and purified on a Gilson HPLC (Xbridge Prep C18 column: 19×100 mm) eluting at 20 mL per min with a linear gradient running from 10% CH3CN/H2O (0.1% NH4OH) to 70% CH3CN/H2O (0.1% NH4OH) over 15 min. The fractions containing the title compound were concentrated under a stream of nitrogen at 50° C. to give 5.2 mg of the title compound (23%).

المصدر