Acetic Acid → N-(3-(5-fluoro-1-methylindolin-6-yl)-1-isopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1-methylpiperidine-4-sulfonamide

HRID 331064Notes

Reaction equation

HRID 331064 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[C:12]1[C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3[NH:21][S:22]([CH:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)(=[O:24])=[O:23])[N:14]([CH:31]([CH3:33])[CH3:32])[CH:13]=1)[N:8]([CH3:34])[CH2:7][CH2:6]2.[C:35](O)(=O)C.C=O.C([BH3-])#N.[Na+]>CO>[F:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[C:12]1[C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3[NH:21][S:22]([CH:25]3[CH2:30][CH2:29][N:28]([CH3:35])[CH2:27][CH2:26]3)(=[O:24])=[O:23])[N:14]([CH:31]([CH3:32])[CH3:33])[CH:13]=1)[N:8]([CH3:34])[CH2:7][CH2:6]2

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 131731993N-(3-(5-fluoro-1-methylindolin-6-yl)-1-isopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidine-4-sulfonamide, hydrochloride

Product 1

HCID 71090323N-(3-(5-fluoro-1-methylindolin-6-yl)-1-isopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1-methylpiperidine-4-sulfonamideYield 35.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of N-(3-(5-fluoro-1-methylindolin-6-yl)-1-isopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidine-4-sulfonamide, hydrochloride (D39) (248 mg, 0.488 mmol) in MeOH (8 mL) at RT was added acetic acid (0.279 mL, 4.88 mmol), formaldehyde (37% solution in water) (0.218 mL, 2.93 mmol) and sodium cyanoborohydride (307 mg, 4.88 mmol). The reaction mixture was stirred at RT for an hour. The reaction mixture was concentrated in vacuo. The residue was passed through SCX cartridge (eluted with MeOH followed by 2M NH3 in MeOH solution; 100 mL each). The basic fractions were concentrated in vacuo to afford a material which was purified using chromatography on silica, eluted with 0-10% MeOH in DCM to afford the title compound (84 mg). LCMS (A): m/z (M+H)+ 486, C25H32FN5O2S requires 485 (acidic).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. washThe residue was passed through SCX cartridge (eluted with MeOH followed by 2M NH3 in MeOH solution; 100 mL each)
  3. concentrationThe basic fractions were concentrated in vacuo
  4. customto afford a material which
  5. customwas purified
  6. washeluted with 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-82a80fd1982441b9bbe3a7826a3d9324
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

Loading…