Sodium hydride → HCID 90387270, compound

HRID 1476851Notes

Reaction equation

HRID 1476851 reaction equation
[OH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.[H-].[Na+].Cl[C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[C:19]([C:27]#[N:28])[N:18]=1>CN1C(=O)CCC1.O>[C:27]([C:19]1[N:18]=[C:17]([O:1][C@H:2]2[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]2)[C:26]2[C:21]([CH:20]=1)=[CH:22][CH:23]=[CH:24][CH:25]=2)#[N:28]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 854055tert-Butyl (3S)-3-hydroxypyrrolidine-1-carboxylateHCID 22250128HCID 22250128, compound

Product 1

HCID 90387270HCID 90387270, compoundYield 55.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
160 °C

Procedure

To (S)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate (1.906 g, 10.18 mmol) in NMP (10 mL) at 0° C. was added NaH (0.339 g, 8.48 mmol). The mixture was stirred for 5 minutes and then 1-chloroisoquinoline-3-carbonitrile (1.6 g, 8.48 mmol) was added. The reaction mixture was heated at 160° C. for 30 minutes in a microwave reactor and was subsequently diluted with water and extracted with EtOAc (2×). The organic phase was dried over Na2SO4 and concentrated. The crude product was purified by silica column chromatography eluting with a gradient of 0-75% EtOAc in hexane to give the title compound as a yellow solid (1.61 g, 55.9%). ESI-MS m/z [M+H-tert-butyl]+ 284.2.

Workup

  1. extractionextracted with EtOAc (2×)
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated
  4. customThe crude product was purified by silica column chromatography
  5. washeluting with a gradient of 0-75% EtOAc in hexane

Sources & evidence

ORD record
ord-4c895aafea0c408da0647b986ddb8951
Source dataset
uspto-grants-2016_08
Patent number
US09402841B2

Reaction notes

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