Triethylamine → HCID 118160616, compound

HRID 1048868Notes

Reaction equation

HRID 1048868 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12]([CH2:13][C@H:14]([NH:18][C:19](=[O:30])[CH2:20][CH2:21][NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:15](O)=[O:16])=[CH:11][N:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:31]([NH:34][C@@H:35]([CH2:39][SH:40])[C:36]([NH2:38])=[O:37])(=[O:33])[CH3:32].C(N(CC)CC)C.CCCP(=O)=O.CCOC(C)=O.C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O>[C:31]([NH:34][C@H:35]([C:36]([NH2:38])=[O:37])[CH2:39][S:40][C:15](=[O:16])[C@@H:14]([NH:18][C:19](=[O:30])[CH2:20][CH2:21][NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:13][C:12]1[N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH:9]=[N:10][CH:11]=1)(=[O:33])[CH3:32]

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 10176265N-Acetylcysteine amideHCID 16167369Propylphosphoric anhydrideHCID 89932196HCID 89932196, compound

Product 1

HCID 118160616HCID 118160616, compoundYield 74.3%

Reagents, catalysts & solvents 1

HCID 21939870Tetrahydrofuran ethyl acetateSolvent

Procedure

To a stirring suspension at room temperature under N2 of (S)-3-(1-(tert-butoxycarbonyl)-1H-imidazol-5-yl)-2-(3-(tert-butoxycarbonylamino)propanamido)propanoic acid (45c, 35.74 g, 83.80 mmol) and (R)-2-acetamido-3-mercaptopropanamide (45b, 13.59 g, 83.78 mmol) in 500 mL of THF:EtOAc (1:1) was added dropwise triethylamine (26 mL, 186 mmol). After addition, the suspension was stirred for 15 minutes then propylphosphonic anhydride, 50 wt. % solution in EtOAc (55 mL, 92 mmol) was added dropwise. The resultant cloudy solution was stirred at room temperature for 2 h then saturated NaHCO3 solution (˜500 mL) was added. The layers were separated and the organic extract was washed with saturated KH2PO4 and then saturated NaCl solution. The aqueous phases were back extracted (in the same order) with fresh EtOAc (2×500 mL). The combined organic extracts were dried using MgSO4, filtered, concentrated and chromatographed twice (silica gel, 50% THF in EtOAc) to give 35.53 g (74%) of tert-butyl 5-((S)-3-((R)-2-acetamido-3-amino-3-oxopropylthio)-2-(3-(tert-butoxycarbonylamino)propanamido)-3-oxopropyl)-1H-imidazole-1-carboxylate (45d) as white foamy solid. MS (APCI) m/z 571 [M+H]+.

Workup

  1. additionAfter addition
  2. stirringThe resultant cloudy solution was stirred at room temperature for 2 h
  3. customThe layers were separated
  4. extractionthe organic extract
  5. washwas washed with saturated KH2PO4
  6. extractionThe aqueous phases were back extracted (in the same order) with fresh EtOAc (2×500 mL)
  7. customThe combined organic extracts were dried
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customchromatographed twice (silica gel, 50% THF in EtOAc)

Sources & evidence

ORD record
ord-38c221fc2d3b4e1cafbfb9cb3a65efd5
Source dataset
uspto-grants-2016_07
Patent number
US09382211B2

Reaction notes

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