Triethylamine → (R)-alpha-[(2-t-Butoxycarbonylamino-2-methyl-1-oxopropyl)amino]-N-[[(2'-nitro)[1,1'-biphenyl]-4-yl]methyl]-1H-indole-3-propanamide

HRID 1910Notes

Reaction equation

HRID 1910 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:28])([CH3:27])[C:10]([NH:12][C@H:13]([CH2:17][C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[NH:20][CH:19]=1)[C:14](O)=[O:15])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:29][CH2:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[N+:43]([O-:45])=[O:44])=[CH:33][CH:32]=1.C(N(CC)CC)C>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C:9]([CH3:28])([CH3:27])[C:10]([NH:12][C@H:13]([CH2:17][C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[NH:20][CH:19]=1)[C:14]([NH:29][CH2:30][C:31]1[CH:32]=[CH:33][C:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[N+:43]([O-:45])=[O:44])=[CH:35][CH:36]=1)=[O:15])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 15895387(R)-2-(2-((tert-Butoxycarbonyl)amino)-2-methylpropanamido)-3-(1H-indol-3-yl)propanoic acidHCID 196928864-Aminomethyl-2'-nitro-1,1'-biphenyl

Product 1

HCID 22883359(R)-alpha-[(2-t-Butoxycarbonylamino-2-methyl-1-oxopropyl)amino]-N-[[(2'-nitro)[1,1'-biphenyl]-4-yl]methyl]-1H-indole-3-propanamideYield 56.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The acid (338 mg, 0.87 mmol) from Step D and 4-aminomethyl-2'-nitro-1,1'-biphenyl (200 mg, 0.87 mmol) and triethylamine (0.245 mL, 1.76 mmol) were dissolved in methylene chloride (8 mL) and stirred at room temperature. Benzotriazolyl-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (388 mg, 0.87 mmol) was added in a single portion. The reaction mixture was stirred together for 3.5 hours then the reaction was quenched by adding saturated aqueous sodium chloride (10 mL) and extracted with methylene chloride (3×20 mL). The combined extracts were dried over magnesium sulfate, filtered and evaporated under vacuum. The resulting thick gum was chromatographed on silica gel using ethyl acetate/hexanes (1:2 v/v) to give 297 mg (50%) of an orange semi-solid.

Workup

  1. stirringThe reaction mixture was stirred together for 3.5 hours
  2. customthe reaction was quenched
  3. additionby adding saturated aqueous sodium chloride (10 mL)
  4. extractionextracted with methylene chloride (3×20 mL)
  5. dry with materialThe combined extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated under vacuum
  8. customThe resulting thick gum was chromatographed on silica gel

Sources & evidence

ORD record
ord-27a0a2a0c29c44ca8129b0684f542de9
Source dataset
uspto-grants-1998_03
Patent number
US05726319

Reaction notes

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