Trifluoroacetic acid → 6'-(3-cyclopropyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)-1'-methylspiro[azetidine-3,3'-indolin]-2'-one

HRID 2209160Notes

Reaction equation

HRID 2209160 reaction equation
C(O)(C(F)(F)F)=O.[CH:8]1([N:11]2[C:15]3[C:16]([O:41][C@@H:42]([C@@H:44]4[CH2:48][C:47](=[O:49])[NH:46][CH2:45]4)[CH3:43])=[N:17][C:18]([C:20]4[CH:28]=[C:27]5[C:23]([C:24]6([CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31]6)[C:25](=[O:30])[N:26]5[CH3:29])=[CH:22][CH:21]=4)=[CH:19][C:14]=3[N:13]=[CH:12]2)[CH2:10][CH2:9]1>ClCCl.CO>[CH:8]1([N:11]2[C:15]3[C:16]([O:41][C@@H:42]([C@@H:44]4[CH2:48][C:47](=[O:49])[NH:46][CH2:45]4)[CH3:43])=[N:17][C:18]([C:20]4[CH:28]=[C:27]5[C:23]([C:24]6([CH2:31][NH:32][CH2:33]6)[C:25](=[O:30])[N:26]5[CH3:29])=[CH:22][CH:21]=4)=[CH:19][C:14]=3[N:13]=[CH:12]2)[CH2:10][CH2:9]1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 117843026tert-butyl 6'-(3-cyclopropyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)-1'-methyl-2'-oxospiro[azetidine-3,3'-indoline]-1-carboxylate

Product 1

HCID 1178437396'-(3-cyclopropyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)-1'-methylspiro[azetidine-3,3'-indolin]-2'-oneYield 21.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

TFA (1.3 mL) was added to a solution of tert-butyl 6′-(3-cyclopropyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)-1′-methyl-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate 3.84 (53 mg, 0.09 mmol) in dichloromethane (5 mL). After two hours, reaction mixture was concentrated under reduced pressure and resulting residue was taken up in 1.5 mL methanol and loaded onto an Agilent StratoSpheres™ PL-HCO3 MP Resin neutralization column (pre-conditioned with methanol). Column was washed with methanol and collected liquids were concentrated under reduced pressure to yield 6′-(3-cyclopropyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)-1′-methylspiro[azetidine-3,3′-indolin]-2′-one 3.85 (9 mg).

Workup

  1. customreaction mixture
  2. concentrationwas concentrated under reduced pressure
  3. customresulting residue
  4. washColumn was washed with methanol
  5. customcollected liquids
  6. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-ee89b439fd6d4dba84b6d1beb98f4d70
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

Loading…