Triethylamine → N-((1R)-4-Amino-1-{[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]methyl}-4-oxobutyl)-3-chloro-4-[(1-methylethyl)oxy]benzamide

HRID 222901Notes

Reaction equation

HRID 222901 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]([NH:14][C@@H:15]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[N:29]=[C:30]4[C:35]([CH3:36])=[CH:34][CH:33]=[CH:32][N:31]4[CH:37]=3)=[CH:24][CH:23]=2)[CH2:16][CH2:17][C:18]([OH:20])=O)=[O:13])[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].C([N:40](CC)CC)C.ClC(OCC)=O>C1COCC1>[NH2:40][C:18](=[O:20])[CH2:17][CH2:16][C@@H:15]([NH:14][C:12](=[O:13])[C:4]1[CH:5]=[CH:6][C:7]([O:8][CH:9]([CH3:10])[CH3:11])=[C:2]([Cl:1])[CH:3]=1)[CH2:21][C:22]1[CH:23]=[CH:24][C:25]([C:28]2[N:29]=[C:30]3[C:35]([CH3:36])=[CH:34][CH:33]=[CH:32][N:31]3[CH:37]=2)=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 67278023HCID 67278023, compound

Product 1

HCID 57594405N-((1R)-4-Amino-1-{[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]methyl}-4-oxobutyl)-3-chloro-4-[(1-methylethyl)oxy]benzamideYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (4R)-4-[({3-chloro-4-[(1-methylethyl)oxy]phenyl}carbonyl)amino]-5-[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]pentanoic acid (900 mg, 1.73 mmol) in anhydrous THF (12.4 mL) at 0° C. under nitrogen was added triethylamine (242 uL, 1.73 mmol) followed by ethyl chloroformate (174 uL, 1.82 mmol). The reaction was stirred for 40 min at 0° C. and then the solids were filtered and washed with 5 mL THF. The filtrate was added to a flask containing NH4OH (5 mL) at room temperature and the reaction mixture was stirred for 1 hour. The product was extracted from the reaction mixture with EtOAc (50 mL). The aqueous layer was extracted with EtOAc (20 mL) and then acidified with 1N HCl solution (30 mL) and re-extracted with EtOAc (10 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo to give a white solid. Purification by recrystallization from hot isopropanol afforded the title compound as a white solid (90%). ESMS [M+H]+=519.4.

Workup

  1. filtrationthe solids were filtered
  2. washwashed with 5 mL THF
  3. additionThe filtrate was added to a flask
  4. additioncontaining NH4OH (5 mL) at room temperature
  5. stirringthe reaction mixture was stirred for 1 hour
  6. extractionThe product was extracted from the reaction mixture with EtOAc (50 mL)
  7. extractionThe aqueous layer was extracted with EtOAc (20 mL)
  8. extractionre-extracted with EtOAc (10 mL)
  9. dry with materialThe combined organic layers were dried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customto give a white solid
  12. customPurification
  13. customby recrystallization from hot isopropanol

Sources & evidence

ORD record
ord-59b70d10962b4ad497ea8adcdffdb728
Source dataset
uspto-grants-2012_06
Patent number
US08207340B2

Reaction notes

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