Sodium Hydroxide → tert-butyl (3R)-3-(4-(1-methyl-5-(2H-tetrazol-5-yl)-1H-pyrazol-4-yl)-N-(3-methylpyridin-2-yl)benzamido)piperidine-1-carboxylate

HRID 588382Notes

Reaction equation

HRID 588382 reaction equation
[CH3:1][C:2]1[C:3]([N:8]([C:22](=[O:38])[C:23]2[CH:28]=[CH:27][C:26](B3OC(C)(C)C(C)(C)O3)=[CH:25][CH:24]=2)[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)=[N:4][CH:5]=[CH:6][CH:7]=1.I[C:40]1[CH:41]=[N:42][N:43]([CH3:50])[C:44]=1[C:45]1[N:46]=[N:47][NH:48][N:49]=1.[OH-].[Na+].CCCCP(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2>CC([O-])=O.CC([O-])=O.[Pd+2].C1(C)C=CC=CC=1.O1CCOCC1>[CH3:50][N:43]1[C:44]([C:45]2[N:49]=[N:48][NH:47][N:46]=2)=[C:40]([C:26]2[CH:27]=[CH:28][C:23]([C:22]([N:8]([C@@H:9]3[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]3)[C:3]3[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=3)=[O:38])=[CH:24][CH:25]=2)[CH:41]=[N:42]1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 1176528035-(4-iodo-1-methyl-1H-pyrazol-5-yl)-2H-tetrazoleHCID 123439813Tert-butyl (R)-3-(N-(3-methylpyridin-2-YL)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)benzamido)piperidine-1-carboxylate

Product 1

HCID 117661189tert-butyl (3R)-3-(4-(1-methyl-5-(2H-tetrazol-5-yl)-1H-pyrazol-4-yl)-N-(3-methylpyridin-2-yl)benzamido)piperidine-1-carboxylateYield 90.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a round-bottom flask charged with a stir bar was added Preparation 24, tert-butyl (3R)-3-{(3-methylpyridin-2-yl)[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl]amino}piperidine-1-carboxylate (1.53 g, 2.93 mmol) and Preparation 22, 5-(4-iodo-1-methyl-1H-pyrazol-5-yl)-2H-tetrazole (674 mg, 2.44 mmol). To this was added dioxane (12.2 mL) and aqueous NaOH (4.07 mL, 3M solution, 12.2 mmol). The reaction mixture was heated to 70° C. under nitrogen atmosphere for 30 min. To a microwave vial was added the Pd(OAc)2 (34.3 mg, 0.153 mmol) and Catacxium A (123 mg, 0.342 mmol). The atmosphere was exchanged for nitrogen, and toluene was added. The catalyst was stirred at room temperature for 15 min, until a bright yellow slurry formed. At this point, the catalyst was added to the reaction mixture, and the temperature was adjusted to 100° C. The reaction mixture was stirred for 3 h at 100° C. After complete consumption of the starting material, the reaction was concentrated under reduced pressure. H2O (10 mL) was added. The reaction mixture was extracted with MTBE (3×25 mL). The aq. phase was cooled to 0° C., and 1M HCl was added dropwise to form a precipitate which was collected via suction filtration and dried in vacuo to obtain tert-butyl (3R)-3-(4-(1-methyl-5-(2H-tetrazol-5-yl)-1H-pyrazol-4-yl)-N-(3-methylpyridin-2-yl)benzamido)piperidine-1-carboxylate (1.2 g, 90%).

Workup

  1. additionTo a round-bottom flask charged with a stir bar
  2. additionwas added
  3. additionwas added
  4. customformed
  5. additionAt this point, the catalyst was added to the reaction mixture
  6. customwas adjusted to 100° C
  7. stirringThe reaction mixture was stirred for 3 h at 100° C
  8. customAfter complete consumption of the starting material
  9. concentrationthe reaction was concentrated under reduced pressure
  10. additionH2O (10 mL) was added
  11. extractionThe reaction mixture was extracted with MTBE (3×25 mL)
  12. temperatureThe aq. phase was cooled to 0° C.
  13. addition1M HCl was added dropwise
  14. customto form a precipitate which
  15. filtrationwas collected via suction filtration
  16. customdried in vacuo

Sources & evidence

ORD record
ord-c54447c87fc54e97840ce39c85f5a308
Source dataset
uspto-grants-2016_01
Patent number
US09227956B2

Reaction notes

Loading…