Aminoisobutyric acid → 2-[(3,5-Bis-benzyloxy-pyridine-2-carbonyl)-amino]-2-methylpropionic acid methyl ester

HRID 1908295Notes

Reaction equation

HRID 1908295 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:23](O)=[O:24])=[N:11][CH:12]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:26]N(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH2:47][C:48]([CH3:53])([CH3:52])[C:49]([OH:51])=[O:50].C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH3:26][O:50][C:49](=[O:51])[C:48]([NH:47][C:23]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:14][C:13]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[CH:12][N:11]=1)=[O:24])([CH3:53])[CH3:52]

Participants

7

Reactant 5

HCID 6119Aminoisobutyric acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 534879953,5-Bis(benzyloxy)picolinic acid

Product 1

HCID 595130922-[(3,5-Bis-benzyloxy-pyridine-2-carbonyl)-amino]-2-methylpropionic acid methyl esterYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3,5-bis-benzyloxy-pyridine-2-carboxylic acid, 2, (1.0 g, 2.99 mmol) in DMF (20 mL) at room temperature under N2 is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) (0.925 g, 5.97 mmol) and 1-hydroxybenzotriazole (HOBt) (0.806 g, 5.97 mmol). The mixture is stirred for 15 minutes after which α-aminoisobutyric acid (0.917 g, 5.97 mmol) and diisopropylethyl-amine (DIPEA) (1.56 mL, 8.96 mmol) are added. The resulting solution is stirred at room temperature for 16 hours then concentrated under reduced pressure. The resulting brown oil is purified over silica (EtOAc:heptane 1:1) to afford 0.58 g (45% yield) of the desired compound as a colorless solid. 1H NMR (250 MHz, CDCl3) δ ppm 8.13 (1H, s), 8.02 (1H, d, J=2.3 Hz), 7.31-7.48 (10H, m), 6.90 (1H, d, J=2.3 Hz), 5.19 (2H, s), 5.10 (2H, s), 3.74 (3H, s), 1.58 (6H, s). HPLC-MS: m/z 435 [M+H]+.

Workup

  1. additionare added
  2. concentrationthen concentrated under reduced pressure
  3. customThe resulting brown oil is purified over silica (EtOAc:heptane 1:1)

Sources & evidence

ORD record
ord-1ca9e7364ee44516bb500fc1683267f4
Source dataset
uspto-grants-2013_12
Patent number
US08598210B2

Reaction notes

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