Methyl iodide → HCID 71140764, compound

HRID 629899Notes

Reaction equation

HRID 629899 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]3[OH:28])=[CH:12][CH:13]=2)[N:8]([CH3:29])[S:7]1(=[O:31])=[O:30].[CH2:33]1COCC1.[H-].[Na+].IC>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]([CH3:27])([CH3:25])[CH3:26])=[O:22])[CH2:17][CH:16]3[O:28][CH3:33])=[CH:12][CH:13]=2)[N:8]([CH3:29])[S:7]1(=[O:31])=[O:30]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 71136667HCID 71136667, compound

Product 1

HCID 71140764HCID 71140764, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a 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) (54 mg, 0.114 mmol), & anhydrous THF (2.5 mL). The reaction mixture was cooled to 0 C while stirring under an atmosphere of nitrogen, then added sodium hydride (60% by wt in mineral oil) (5.92 mg, 0.148 mmol) in one portion. Reaction mixture was continued to stir at 0 C for 10 minutes, then added iodomethane (8.54 μl, 0.137 mmol) and 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-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazole-[3,4-b]pyridin-5-yl}-3-methoxypiperidine-1-carboxylate (28-1). HRMS (M+H)+: observed=489.1983, calculated=489.1978.

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-7571578701f74b5ebef252f0ae2b891d
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

Loading…