4-Amino-1-Boc-piperidine → 1,1-Dimethylethyl 4-(7-cyano-1,3-dihydro-1-oxo-2H-isoindol-2-yl)-1-piperidinecarboxylate

HRID 1097978Notes

Reaction equation

HRID 1097978 reaction equation
Br[CH2:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]#[N:14])[C:4]=1[C:5](OC)=[O:6].[NH2:15][CH:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1>O1CCCC1.CN(C=O)C>[C:13]([C:9]1[CH:10]=[CH:11][CH:12]=[C:3]2[C:4]=1[C:5](=[O:6])[N:15]([CH:16]1[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:20][CH2:21]1)[CH2:2]2)#[N:14]

Participants

5

Reactant 2

HCID 12682914-Amino-1-Boc-piperidineHCID 66812920HCID 66812920, compound

Product 1

HCID 668126151,1-Dimethylethyl 4-(7-cyano-1,3-dihydro-1-oxo-2H-isoindol-2-yl)-1-piperidinecarboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of EXAMPLE 6C (300 mg) in tetrahydrofuran (2 mL) and N,N′-dimethylformamide (2 mL) was added tert-butyl 4-aminopiperidine-1-carboxylate (320 mg,) in N,N′-dimethylformamide (2 mL) and tetrahydrofuran (2 mL) at −40° C. The solution was warmed to ambient temperature over 2 hours, and stirred for 16 hours. The solvent was removed, and the concentrate was partitioned between ethyl acetate and water. The extract was washed with brine and concentrated, and the concentrate was purified by flash chromatography on silica gel with 80% ethyl acetate in hexanes.

Workup

  1. customThe solvent was removed
  2. customthe concentrate was partitioned between ethyl acetate and water
  3. washThe extract was washed with brine
  4. concentrationconcentrated
  5. customthe concentrate was purified by flash chromatography on silica gel with 80% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d66f2dfb232349c19618d4d8d792bef2
Source dataset
uspto-grants-2012_03
Patent number
US08143284B2

Reaction notes

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