Ammonium Hydroxide → HCID 86707417, compound

HRID 338851Notes

Reaction equation

HRID 338851 reaction equation
[NH:1]1[CH2:5][CH2:4][C@H:3]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH2:2]1.[C:14]([C:18]1[CH:19]=[CH:20][CH:21]=[C:22]2[C:27]=1[N:26]=[C:25]([C:28]1[N:32]3[CH:33]=[C:34]([C:37](=O)[CH3:38])[CH:35]=[CH:36][C:31]3=[N:30][N:29]=1)[CH:24]=[CH:23]2)([CH3:17])([CH3:16])[CH3:15].[BH4-].[Na+].[OH-].[NH4+]>C1COCC1.C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C.C(OCC)(=O)C.O.C(O)C>[C:14]([C:18]1[CH:19]=[CH:20][CH:21]=[C:22]2[C:27]=1[N:26]=[C:25]([C:28]1[N:32]3[CH:33]=[C:34]([CH:37]([N:1]4[CH2:5][CH2:4][C@H:3]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:10])([CH3:12])[CH3:11])[CH2:2]4)[CH3:38])[CH:35]=[CH:36][C:31]3=[N:30][N:29]=1)[CH:24]=[CH:23]2)([CH3:17])([CH3:16])[CH3:15]

Participants

10

Reactant 4

HCID 14923Ammonium HydroxideHCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 4311764Sodium borohydrideHCID 70984268HCID 70984268, compound

Product 1

HCID 86707417HCID 86707417, compoundYield 69.9%

Reagents, catalysts & solvents 5

HCID 178460666HCID 178460666, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-tert-butyl pyrrolidin-3-ylcarbamate (0.502 g, 2.69 mmol), 1-(3-(8-tert-butylquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethanone (0.464 g, 1.35 mmol) in THF (20 mL) was added tetraisopropoxytitanium (0.79 mL, 2.69 mmol) and the reaction mixture was stirred at ambient temperature for 18 hours. Ethanol (2 mL) and NaBH4 (0.204 g, 5.39 mmol) were added and the mixture was stirred at ambient temperature for 2 hours. Water (10 mL), concentrated ammonium hydroxide (2 mL) and ethyl acetate (20 mL) were added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 25M column, 0-90% CH3CN/water gradient; 25 CV) to give tert-butyl (3S)-1-(1-(3-(8-tert-butylquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamate (0.485 g, 69.9%) as solid.

Workup

  1. stirringthe mixture was stirred at ambient temperature for 2 hours
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit

Sources & evidence

ORD record
ord-9a9d650b8eb84fbab1d25f54ac1c974f
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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