1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-[[3,5-Bis(phenylmethoxy)-2-pyridinyl]carbonyl]glycine methyl ester

HRID 1797989Notes

Reaction equation

HRID 1797989 reaction equation
Cl.[CH2:2]([O:9][C:10]1[C:11]([C:24](O)=[O:25])=[N:12][CH:13]=[C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:15]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(C(C)C)CC)(C)C.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.Cl.[CH3:58][O:59][C:60](=[O:63])[CH2:61][NH2:62]>CN(C=O)C>[CH3:58][O:59][C:60](=[O:63])[CH2:61][NH:62][C:24]([C:11]1[C:10]([O:9][CH2:2][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)=[CH:15][C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:13][N:12]=1)=[O:25]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 122755Glycine methyl ester hydrochlorideHCID 67212265HCID 67212265, compound

Product 1

HCID 59030679N-[[3,5-Bis(phenylmethoxy)-2-pyridinyl]carbonyl]glycine methyl esterYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3,5-bis-benzyloxy-pyridine-2-carboxylic acid HCl, 2, (8.06 g, 21.7 mmol) in DMF (100 mL) at 0° C. under N2 is added diisopropylethylamine (11.35 mL, 65.1 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) (6.23 g, 32.6 mmol) and 1-hydroxybenzotriazole (HOBt) (0.294 g, 2.2 mmol). The solution is stirred for 5 minutes and glycine methyl ester hydrochloride (4.09 g, 32.6 mmol) is added. The reaction is allowed to warm slowly to room temperature and stirred 3 days. The reaction volume is partially concentrated under reduced pressure then diluted with EtOAc and washed with saturated aqueous NaHCO3 and saturated aqueous NaCl. The organic layer is dried (MgSO4), filtered and concentrated under reduced pressure to afford a yellow oil that is purified over silica (EtOAc:heptane gradient 1:1 to 1:0) to afford 3.5 g (40% yield) of the desired product as a yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.12 (1 H, t, J=4.9 Hz), 7.95 (1 H, d, J=1.8 Hz), 7.38-7.44 (2 H, m), 7.22-7.35 (8 H, m), 6.85 (1 H, d, J=2.6 Hz), 5.14 (2 H, s), 5.03 (2 H, s), 4.18 (2 H, d, J=5.5 Hz), 3.69 (3 H, s). HPLC-MS: m/z 407 [M+H]+.

Workup

  1. stirringstirred 3 days
  2. concentrationThe reaction volume is partially concentrated under reduced pressure
  3. additionthen diluted with EtOAc
  4. washwashed with saturated aqueous NaHCO3 and saturated aqueous NaCl
  5. dry with materialThe organic layer is dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto afford a yellow oil that
  9. customis purified over silica (EtOAc:heptane gradient 1:1 to 1:0)

Sources & evidence

ORD record
ord-fb9eb3f54aa84c98b18676fc59671155
Source dataset
uspto-grants-2013_01
Patent number
US08343952B2

Reaction notes

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