Dicyclohexylcarbodiimide → Methyl N-((7-Methyl-1,8-naphthyridin-2(1H)-on-3-yl)acetyl)-N-(2-(tert-butyloxycarbonyl)aminoethyl)glycinate

HRID 987899Notes

Reaction equation

HRID 987899 reaction equation
[CH3:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]=[C:7]([CH2:13][C:14]([OH:16])=O)[C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1.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][CH2:47]C)=[O:45])=[O:38])([CH3:35])([CH3:34])[CH3:33]>CN(C=O)C>[CH3:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]=[C:7]([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:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 4319362Ethyl N-{2-[(tert-butoxycarbonyl)amino]ethyl}glycinateHCID 22987109(7-methyl-1,8-naphthyridin-2(1H)-on-3-yl)acetic acid

Product 1

HCID 22987110Methyl N-((7-Methyl-1,8-naphthyridin-2(1H)-on-3-yl)acetyl)-N-(2-(tert-butyloxycarbonyl)aminoethyl)glycinateYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a precooled (0° C.) solution of (7-methyl-1,8-naphthyridin-2(1H)-on-3-yl)acetic acid (0.995 g, 4.60 mmol) and DhbtOH (0.744 g, 4.60 mmol) in DMF (25 mL)was added DCC (1.04 g, 5.00 mmol) and the mixture was stirred for 40 min at 0° before addition of ethyl N-(2-(tert-butyloxycarbonyl)aminoethyl)glycinate (1.10 g, 5.0 mmol). This mixture was stirred at rt overnight, evaporated in vacuo, redissolved in ethyl acetate (75 mL) and washed with 5% aqueous NaHCO3 (3×25 mL) and with brine (2×25 mL). The organic phase was dried over MgSO4, filtered and evaporated in vacuo. The crude product purified on silica using dichloromethane/methanol (90:10 v/v) as the eluent. Fractions containing the product were pooled and evaporated in vacuo to yield the desired product (790 mg, 41%) (mp 98-100° C.). 1H NMR (DMSO-d6; this compound exist as two rotamers; chemical shifts for the minor rotamer is given in brackets): δ 12.05 (s br, 1H), 7.91 (7.96) (d, 8.0 Hz, 1H), 7.74 (7.71) (s, 1H), 7.10 (d, 8.0 Hz, 1H), 6.90 (6.99) (m, 1H), 4.05 (4.36) (s, 2H), 4.09 (q, J=5.2 Hz, 3H), 3.63 (s, 3H), 3.47 (m, 2H), 3.17 (s, 2H), 3.16 (s, 3H), 1.36 (1.35) (s, 9H). 13C NMR (DMSO-d6): δ 170.44 (170.66), 170.11, 162.65 (162.73), 159.22, 155.83 (155.71), 148.99, 136.43 (136.77), 136.04 (136.17), 128.61 (128.29), 118.21, 112.00 (112.07), 78.04, 51.81 (52.20), 47.63 (48.20), 38.59 (38.45), 33.42 (33.75), 28.27, 24.22. FAB+ HRMS: 433.2086, calc. C21H29N4O6 433.2087.

Workup

  1. customevaporated in vacuo
  2. dissolutionredissolved in ethyl acetate (75 mL)
  3. washwashed with 5% aqueous NaHCO3 (3×25 mL) and with brine (2×25 mL)
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe crude product purified on silica
  8. additionFractions containing the product
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-60efcd5a04b2465d9fca89f753c34acf
Source dataset
uspto-grants-2003_10
Patent number
US06632919B1

Reaction notes

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