tert-butyl (3S)-3-aminopiperidine-1-carboxylate → (S)-tert-Butyl 3-(1-(4-Methoxybenzyl)-1H-indazol-5-ylamino)piperidine-1-carboxylate

HRID 656535Notes

Reaction equation

HRID 656535 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)[N:6]=[CH:5]2.[NH2:20][C@H:21]1[CH2:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][N:7]2[C:8]3[C:4](=[CH:3][C:2]([NH:20][C@H:21]4[CH2:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22]4)=[CH:10][CH:9]=3)[CH:5]=[N:6]2)=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 1501975tert-butyl (3S)-3-aminopiperidine-1-carboxylateHCID 23676156Sodium t-butoxideHCID 442405275-Bromo-1-(4-methoxybenzyl)-1H-indazole

Product 1

HCID 66761062(S)-tert-Butyl 3-(1-(4-Methoxybenzyl)-1H-indazol-5-ylamino)piperidine-1-carboxylateYield 83.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-bromo-1-(4-methoxybenzyl)-1H-indazole (870 mg, 2.75 mmol) in toluene (10 mL) was added in succession (S)-tert-butyl 3-aminopiperidine-1-carboxylate (660 mg, 3.3 mmol), sodium tert-butoxide (475 mg, 5 mmol), and rac-(±)-BINAP (180 mg, 0.29 mmol). The flask was evacuated and refilled with nitrogen three times, after which Pd2 dba3 (83 mg, 1.5 mol %) was added. The flask was again purged with nitrogen three times, and was then heated to 80° C. overnight. The solution was cooled to room temperature and then filtered through a pad of celite, washing with additional toluene. The toluene solution was then loaded directly onto a silica gel column that had been packed with heptane. The column was flushed with 2 column volumes of heptane, and then eluted with 40/60—EtOAc/heptane to afford the title compound (1.00 g 82%).

Workup

  1. customThe flask was evacuated
  2. additionrefilled with nitrogen three times
  3. additionafter which Pd2 dba3 (83 mg, 1.5 mol %) was added
  4. customThe flask was again purged with nitrogen three times
  5. temperatureThe solution was cooled to room temperature
  6. filtrationfiltered through a pad of celite
  7. washwashing with additional toluene
  8. customThe column was flushed with 2 column volumes of heptane
  9. washeluted with 40/60—EtOAc/heptane

Sources & evidence

ORD record
ord-e8d901d2516243c3ad599e8619ca2f89
Source dataset
uspto-grants-2011_12
Patent number
US08071779B2

Reaction notes

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