Ethyl Acetate → [3-(6-Methoxy-[1,5]naphthyridin-4-yl)-prop-2-ynyl]-carbamic acid tert-butyl ester

HRID 1640505Notes

Reaction equation

HRID 1640505 reaction equation
[C:1]([NH:8][CH2:9][C:10]#[CH:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Br[C:13]1[CH:14]=[CH:15][N:16]=[C:17]2[C:22]=1[N:21]=[C:20]([O:23][CH3:24])[CH:19]=[CH:18]2.CC(=O)OCC>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:4]([O:3][C:1](=[O:2])[NH:8][CH2:9][C:10]#[C:11][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([O:23][CH3:24])[N:21]=2)[N:16]=[CH:15][CH:14]=1)([CH3:5])([CH3:6])[CH3:7]

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 11073648tert-butyl N-(prop-2-yn-1-yl)carbamateHCID 534216178-Bromo-2-methoxy-1,5-naphthyridine

Product 1

HCID 66737778[3-(6-Methoxy-[1,5]naphthyridin-4-yl)-prop-2-ynyl]-carbamic acid tert-butyl esterYield 44.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-Boc propargyl amine (3.25 g, 20.9 mmol) and 8-bromo-2-methoxy-[1,5]naphthyridine (5.00 g, 20.9 mmol; prepared as in WO 2006/032466) and TEA (17.5 mL, 6 eq.) in DMF (120 mL) were added Pd(PPh3)2Cl2 (755 mg, 1.08 mmol) and CuI (432 mg, 2.27 mmol). The mixture was degassed with a stream of N2 for 15 min and then stirred at rt for 5 h. The mixture was partitioned between water and EA, the org. layer was washed several times with water and a sat. NH4Cl solution, dried over MgSO4 and concentrated. Chromatography on SiO2 (Hex/EA 1:1, EA) gave the coupling product as a beige solid (2.90 g, 44% yield).

Workup

  1. customThe mixture was degassed with a stream of N2 for 15 min
  2. customThe mixture was partitioned between water and EA
  3. washlayer was washed several times with water
  4. dry with materiala sat. NH4Cl solution, dried over MgSO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-709bb9c77d504ad592fefaee9a63f50d
Source dataset
uspto-grants-2012_02
Patent number
US08114867B2

Reaction notes

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