4-Methylmorpholine → 2-Benzyloxycarbonylamino-4-(2-pyrrolo[3,2-c]pyridin-1-yl-acetylamino)-butyric acid methyl ester

HRID 651628Notes

Reaction equation

HRID 651628 reaction equation
[N:1]1([CH2:10][C:11]([OH:13])=O)[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[CH:3]=[CH:2]1.FC(F)(F)C(O)=O.[CH3:21][O:22][C:23](=[O:39])[C@@H:24]([NH:28][C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30])[CH2:25][CH2:26][NH2:27].CN1CCOCC1.O.ON1C2C=CC=CC=2N=N1>CN(C=O)C>[CH3:21][O:22][C:23](=[O:39])[CH:24]([NH:28][C:29]([O:31][CH2:32][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)=[O:30])[CH2:25][CH2:26][NH:27][C:11](=[O:13])[CH2:10][N:1]1[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[CH:3]=[CH:2]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 27960291-Hydroxybenzotriazole hydrateHCID 18176302Pyrrolo[3,2-c]pyridin-1-yl-acetic acidHCID 700234912-(S)-benzyloxycarbonylamino-4-amino-butyric acid methyl ester trifluoroacetate

Product 1

HCID 700232962-Benzyloxycarbonylamino-4-(2-pyrrolo[3,2-c]pyridin-1-yl-acetylamino)-butyric acid methyl esterYield 41.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Pyrrolo[3,2-c]pyridin-1-yl-acetic acid (0.50 g, 1.89 mmol), 2-(S)-benzyloxycarbonylamino-4-amino-butyric acid methyl ester trifluoroacetate (0.93 g, 2.45 mmol), 4-methylmorpholine (0.75 g, 7.41 mmol), and 1-hydroxybenzotriazole hydrate (0.36 g, 2.65 mmol) are dissolved in DMF (11 mL) and the resulting mixture is cooled to 0° C. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiiimide hydrochloride (0.80 g, 4.17 mmol) is added to the solution. The ice bath is removed and the reaction mixture is stirred at room temperature. After 18 hours, the solution is diluted with a saturated solution of NH4Cl and extracted twice with EtOAc. The combined organic layers are washed with H2O, saturated NaHCO3 and saturated NaCl. The organic phase is dried over MgSO4, filtered and concentrated in vacuo. The crude product is purified by column chromatography in a gradient of 3% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2 to afford the title compound (0.33 g, 0.78 mmol) as a solid.

Workup

  1. customThe ice bath is removed
  2. additionthe solution is diluted with a saturated solution of NH4Cl
  3. extractionextracted twice with EtOAc
  4. washThe combined organic layers are washed with H2O, saturated NaHCO3 and saturated NaCl
  5. dry with materialThe organic phase is dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product is purified by column chromatography in a gradient of 3% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-a7cf12e29d43440b8982e8b0bb80ed1a
Source dataset
uspto-grants-2001_08
Patent number
US06281227B1

Reaction notes

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