Methanol → tert-butyl (1-(2-(7-cyano-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate

HRID 656924Notes

Reaction equation

HRID 656924 reaction equation
[O:1]=[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]([C:12]#[N:13])=[CH:5][C:4]=2[N:3]1[CH2:14][CH:15]=O.[C:17]([O:21][C:22]([NH:24][CH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].CO.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[NH3:3].[C:12]([C:6]1[CH:5]=[C:4]2[C:9]([CH:10]=[CH:11][C:2](=[O:1])[N:3]2[CH2:14][CH2:15][N:28]2[CH2:27][CH2:26][CH:25]([NH:24][C:22](=[O:23])[O:21][C:17]([CH3:19])([CH3:18])[CH3:20])[CH2:30][CH2:29]2)=[N:8][CH:7]=1)#[N:13]

Participants

7

Reactant 4

HCID 887MethanolHCID 7238334-(N-Boc-amino)piperidineHCID 5049666Sodium triacetoxyborohydrideHCID 86633192(7-cyano-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehyde

Product 2

HCID 222AmmoniaHCID 71248370tert-butyl (1-(2-(7-cyano-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)carbamateYield 100.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 6-oxo-5-(2-oxoethyl)-5,6-dihydro-1,5-naphthyridine-3-carbonitrile (0.50 g, 2.05 mmol), 4-t-butoxycarbonylaminopiperidine (0.80 g, 4.00 mmol) and 3A molecular sieves in DCM (4.5 ml) and MeOH (4.5 ml) was stirred at rt for 4 h. The mixture was then treated with NaBH(OAc)3 (0.94 g, 4.43 mmol), stirred at rt for 18 h, filtered through a thin pad of celite, evaporated, dissolved in 10% MeOH/DCM and washed with sat. aq NaHCO3. The aqueous phase was re-extracted twice with 10% MeOH/DCM, the combined organics dried, and the residue was subjected to column chromatography on silica gel using a DCM:MeOH:aq NH3 gradient to provide the desired compound (0.411 g, 50%).

Workup

  1. filtrationfiltered through a thin pad of celite
  2. customevaporated
  3. dissolutiondissolved in 10% MeOH/DCM
  4. washwashed with sat. aq NaHCO3
  5. extractionThe aqueous phase was re-extracted twice with 10% MeOH/DCM

Sources & evidence

ORD record
ord-4e6c3988a2c54fda99b1141906caf5ba
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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