Dicyclohexylcarbodiimide → Methyl N-((5-Methyl-1,8-naphthyridin-2(1H)-on-3-yl)acetyl)-N-(2-(tert-butyloxycarbonyl)aminoethyl)glycinate

HRID 987903Notes

Reaction equation

HRID 987903 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([CH2:13][C:14]([OH:16])=O)[C:6](=[O:12])[NH:7]2.C1CCC(N=C=NC2CCCCC2)CC1.[C:32]([O:36][C:37]([NH:39][CH2:40][CH2:41][NH:42][CH2:43][C:44]([O:46][CH3:47])=[O:45])=[O:38])([CH3:35])([CH3:34])[CH3:33]>CN(C=O)C>[CH3:1][C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([CH2:13][C:14]([N:42]([CH2:41][CH2:40][NH:39][C:37]([O:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:38])[CH2:43][C:44]([O:46][CH3:47])=[O:45])=[O:16])[C:6](=[O:12])[NH:7]2

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 10889780Methyl (2-((tert-butoxycarbonyl)amino)ethyl)glycinateHCID 22987112HCID 22987112, compound

Product 1

HCID 22987119Methyl N-((5-Methyl-1,8-naphthyridin-2(1H)-on-3-yl)acetyl)-N-(2-(tert-butyloxycarbonyl)aminoethyl)glycinateYield 33%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a precooled (0° C.) solution of (5-methyl-1,8-naphthyridin-2(1H)-on-3-yl)acetic acid (1.20 g, 5.50 mmol) and DhbtOH (0.987 g, 6.10 mmol) in DMF (25 mL) was added DCC (1.25 g, 6.10 mmol) and the resulting mixture was stirred for 40 min. prior to the addition of methyl N-(2-(tert-butyloxycarbonyl)aminoethyl)glycinate (1.32 g, 6.10 mmol). The mixture was stirred at rt. overnight, evaporated in vacuo, redissolved in ethyl acetate (75 mL) and the DCU filtered off. The organic phase was washed with NaHCO3 (3×25 mL) and with brine (2×25 mL), dried (MgSO4) and evaporated in vacuo. The crude product was purified on silica using MeOH/dichloromethane (95:5 to 90:10 v/v) as the eluent. Fractions containing the product were pooled and evaporated in vacuo. to yield the desired product (752 mg, 33%) (mp 175-77° C.). 1H NMR (DMSO-d6; this compound exists as two rotamers; chemical shifts for the minor rotamer is given in brackets): δ 12.10 (12.08), (s br, 1H), 8.33 (8.33) (d, J=4.8 Hz, 1H), 7.96 (7.90) (s, 1H), 7.09 (d, J=4.8 Hz, 1H), 6.92 (6.70) (m, 1H), 4.07 (4.37) (s, 2H), 3.67 (s, 2H), 3.64 (s, 3H), 3.46 (m, 2H), 3.17 (m, 2H), 2.54 (2.53) (s, 3H), 1.37 (1.35) (s, 9H). 13C NMR (DMSO-d6): δ 170.30 (170.50), 170.04, 162.30, 155.73, 149.47, 149.25, 145.16, 132.92 (133.56), 129.12 (129.28), 119.87, 113.35, 77.97, 52.13, 51.76 (50.12), 47.47 (48.16), 38.98 (38.39), 33.81 (33.99), 28.24, 17.66. FAB+MS (m/z): 433.2087 (M+H+, calc. for C21H28N4O6+H+ 433.2086).

Workup

  1. stirringThe mixture was stirred at rt
  2. customovernight, evaporated in vacuo
  3. dissolutionredissolved in ethyl acetate (75 mL)
  4. filtrationthe DCU filtered off
  5. washThe organic phase was washed with NaHCO3 (3×25 mL) and with brine (2×25 mL)
  6. dry with materialdried (MgSO4)
  7. customevaporated in vacuo
  8. customThe crude product was purified on silica
  9. additionFractions containing the product
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-fa31afff7a6144e6939919b256ce8d9b
Source dataset
uspto-grants-2003_10
Patent number
US06632919B1

Reaction notes

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