Toluene → 1-[(2,2-Difluorocyclopropyl)methyl]-3-methyl-5-[2-methyl-5-(piperazin-1-yl methyl)phenyl]-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide

HRID 515241Notes

Reaction equation

HRID 515241 reaction equation
[F:1][C:2]1([F:39])[CH2:4][CH:3]1[CH2:5][N:6]1[C:14]2[C:9](=[N:10][C:11]([C:15]3[CH:16]=[C:17]([CH:32]=[CH:33][C:34]=3[CH3:35])[CH2:18][N:19]3[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]3)=[CH:12][CH:13]=2)[N:8]([CH3:36])[S:7]1(=[O:38])=[O:37].C(O)(C(F)(F)F)=O.C1(C)C=CC=CC=1>C(Cl)Cl>[F:39][C:2]1([F:1])[CH2:4][CH:3]1[CH2:5][N:6]1[C:14]2[C:9](=[N:10][C:11]([C:15]3[CH:16]=[C:17]([CH2:18][N:19]4[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[CH:32]=[CH:33][C:34]=3[CH3:35])=[CH:12][CH:13]=2)[N:8]([CH3:36])[S:7]1(=[O:38])=[O:37]

Participants

5

Reactant 3

HCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 67412149Tert-butyl 4-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperazine-1-carboxylate

Product 1

HCID 674107481-[(2,2-Difluorocyclopropyl)methyl]-3-methyl-5-[2-methyl-5-(piperazin-1-yl methyl)phenyl]-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tert-butyl 4-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperazine-1-carboxylate (43-1) (3.3 g, 5.7 mmol, 1.0 eq) was dissolved in DCM (40 mL) and TFA (4.4 mL, 56.7 mmol, 10 eq) was added and the reaction mixture stirred at ambient temperature for 45 minutes. Toluene (10 mL) was added and the reaction mixture was concentrated. The residue was dissolved in EtOAc (100 mL) and then washed with sodium bicarbonate (3×20 mL), water (20 mL) and brine (20 mL), dried over MgSO4, filtered and concentrated to afford 1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-[2-methyl-5-(piperazin-1-ylmethyl)phenyl]-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide (43-2) as a tan solid. No further purification was necessary. HRMS m/z (M+H) 463.1925 found, 463.1926 required.

Workup

  1. concentrationthe reaction mixture was concentrated
  2. dissolutionThe residue was dissolved in EtOAc (100 mL)
  3. washwashed with sodium bicarbonate (3×20 mL), water (20 mL) and brine (20 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-fd4dc9f5fd0c44f88fbfe4ac6f838fe0
Source dataset
uspto-grants-2015_08
Patent number
US09108937B2

Reaction notes

Loading…