1,2-Dichloroethane → 3-(4-Hydroxy-2-{[(pyrazine-2-carbonyl)-amino]-methyl}-phenyl)-propionic acid tert-butyl ester

HRID 1181046Notes

Reaction equation

HRID 1181046 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7]([OH:9])=O.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[C:24]([O:28][C:29](=[O:41])[CH2:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][C:33]=1[CH2:39][NH2:40])([CH3:27])([CH3:26])[CH3:25]>C(Cl)Cl.O>[C:24]([O:28][C:29](=[O:41])[CH2:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][C:33]=1[CH2:39][NH:40][C:7]([C:2]1[CH:3]=[N:4][CH:5]=[CH:6][N:1]=1)=[O:9])([CH3:27])([CH3:25])[CH3:26]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 10472-Pyrazinecarboxylic acidHCID 757711-HydroxybenzotriazoleHCID 17984622Tert-butyl-3-[2-(aminomethyl)-4-hydroxyphenyl]propanoate

Product 1

HCID 589790143-(4-Hydroxy-2-{[(pyrazine-2-carbonyl)-amino]-methyl}-phenyl)-propionic acid tert-butyl esterYield 70.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of pyrazine-2-carboxylic acid (0.570 g, 4.60 mmol) in CH2Cl2 (50 mL) was added EDC (0.960 g, 5.01 mmol) and HOBt (0.620 g, 4.60 mmol) at room temperature. The mixture was stirred for 10 min, and 3-(2-aminomethyl-4-hydroxy-phenyl)-propionic acid tert-butyl ester (1.05 g, 4.18 mmol) was added. The reaction mixture was stirred for 18 h at room temperature, treated with water (50 mL), and extracted with CH2Cl2 (2×50 mL). The combined organic layers were dried (Na2SO4), concentrated, and purified by silica gel chromatography (EtOAc/hexanes, 1:1 to 1:0) to obtain the title compound (1.05 g, 70%). 1H NMR (400 MHz, CDCl3): δ 1.40 (s, 9H), 2.52 (t, 2H, J=7.6 Hz), 2.91 (t, 2H, J=7.6 Hz), 4.66 (d, 2H, J=6.4 Hz), 6.73 (dd, 1H, J=2.9, 7.8 Hz), 6.83 (d, 1H, J=2.4 Hz), 7.07 (d, 1H, J=8.3 Hz), 8.17 (br s, 1H), 8.49 (dd, 1H, J=1.5, 2.4 Hz), 8.73 (d, 1H, J=2.4 Hz), 9.41 (d, 1H, J=1.5 Hz). MS (ES) m/z 356.1 ([M−H]−).

Workup

  1. stirringThe reaction mixture was stirred for 18 h at room temperature
  2. extractionextracted with CH2Cl2 (2×50 mL)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. concentrationconcentrated
  5. custompurified by silica gel chromatography (EtOAc/hexanes, 1:1 to 1:0)

Sources & evidence

ORD record
ord-f2e1111105ef463ba52fc8b52d4fe280
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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