Sodium Hydroxide → (R)-tert-butyl 3-(2-(5-(2,6-difluorophenyl)-1H-indol-3-yl)pyrimidin-4-ylamino)piperidine-1-carboxylate

HRID 1529306Notes

Reaction equation

HRID 1529306 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14](S(C1C=CC(C)=CC=1)(=O)=O)[CH:13]=[C:12]2[C:28]1[N:33]=[C:32]([NH:34][C@@H:35]2[CH2:40][CH2:39][CH2:38][N:37]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:36]2)[CH:31]=[CH:30][N:29]=1.[OH-].[Na+]>O1CCOCC1>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[C:28]1[N:33]=[C:32]([NH:34][C@@H:35]2[CH2:40][CH2:39][CH2:38][N:37]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:36]2)[CH:31]=[CH:30][N:29]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67959582(R)-tert-butyl 3-(2-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)pyrimidin-4-ylamino)piperidine-1-carboxylate

Product 1

HCID 67959988(R)-tert-butyl 3-(2-(5-(2,6-difluorophenyl)-1H-indol-3-yl)pyrimidin-4-ylamino)piperidine-1-carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of (R)-tert-butyl 3-(2-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)pyrimidin-4-ylamino)piperidine-1-carboxylate (500 mg, 0.757 mmol) in dioxane (10 mL) was treated with aqueous 1N NaOH (5 mL) and heated at 100° C. for 2 h. The resulting mixture was cooled to RT, and quenched with ice cold water. The resulting precipitate was collected by filtration, washed with ice cold water and dried to obtain the pure (R)-tert-butyl 3-(2-(5-(2,6-difluorophenyl)-1H-indol-3-yl)pyrimidin-4-ylamino)piperidine-1-carboxylate (350 mg, 92%). (R)-tert-butyl 3-(2-(5-(2,6-difluorophenyl)-1H-indol-3-yl)pyrimidin-4-ylamino)piperidine-1-carboxylate (350 mg, 0.69 mmol) was treated with ethanolic HCl (10 mL). The reaction mixture was stirred at RT for 16 h and then extracted with DCM. The combined organic layers were dried; filtered and concentrated to give the crude product, which was purified by recrystallization using 10% MeOH in CHCl3 to yield (R)-2-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-N-(piperidin-3-yl)pyrimidin-4-amine MS (ESI, pos. ion) m/z: 406 (M+1).

Workup

  1. temperatureThe resulting mixture was cooled to RT
  2. customquenched with ice cold water
  3. filtrationThe resulting precipitate was collected by filtration
  4. washwashed with ice cold water
  5. customdried

Sources & evidence

ORD record
ord-b0d7048db6e84859a018b331cfa767b4
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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