Dichloromethane → HCID 71136707, compound

HRID 629900Notes

Reaction equation

HRID 629900 reaction equation
[F:1][C:2]1([F:32])[CH2:4][CH:3]1[CH2:5][N:6]1[C:14]2[C:9](=[N:10][C:11]([CH:15]3[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH:16]3O)=[CH:12][CH:13]=2)[N:8]([CH3:29])[S:7]1(=[O:31])=[O:30].C(Cl)Cl.CCN(S(F)(F)[F:42])CC>CO.O>[F:32][C:2]1([F:1])[CH2:4][CH:3]1[CH2:5][N:6]1[C:14]2[C:9](=[N:10][C:11]([CH:15]3[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:22])[CH2:17][CH:16]3[F:42])=[CH:12][CH:13]=2)[N:8]([CH3:29])[S:7]1(=[O:31])=[O:30]

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 123472(Diethylamino)sulfur trifluorideHCID 71136667HCID 71136667, compound

Product 1

HCID 71136707HCID 71136707, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a round bottom flask was added tert-butyl 4-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-3-hydroxypiperidine-1-carboxylate (27-1) (74 mg, 0.156 mmol), anhydrous DCM (1 mL), the reaction mixture was cooled to 0 C while stirring under an atmosphere of nitrogen, then added DAST (0.035 ml, 0.265 mmol) dropwise. Reaction mixture was continued to stir at 0 C for 10 minutes, then permitted to warm to room temperature. After 1 hour reaction mixture was diluted with MeOH & drops of water, then purified by reverse-phase chromatography (10-100% CH3CN:0.1% TFA in H2O) to yield tert-Butyl 4-{1-[(2,2-difluorocyclopropypmethyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-3-fluoropiperidine-1-carboxylate (29-1). HRMS (M+H)+: observed=477.1785, calculated=477.1778.

Workup

  1. temperaturethe reaction mixture was cooled to 0 C
  2. customReaction mixture
  3. stirringto stir at 0 C for 10 minutes
  4. customAfter 1 hour reaction mixture
  5. custompurified by reverse-phase chromatography (10-100% CH3CN:0.1% TFA in H2O)

Sources & evidence

ORD record
ord-5ee780cb36644358939b0cfd61b348a9
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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