Diisopropylethylamine → (S)-tert-butyl 4'-((5-((1-(4-(tert-butyl)phenyl)ethyl)carbamoyl)-2,3-dimethyl-1H-indol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylate

HRID 1851885Notes

Reaction equation

HRID 1851885 reaction equation
[C:1]([O:5][C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[CH:19]=[CH:18][C:17]([CH2:20][N:21]2[C:29]3[C:24](=[CH:25][C:26]([C:30](O)=[O:31])=[CH:27][CH:28]=3)[C:23]([CH3:33])=[C:22]2[CH3:34])=[CH:16][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl-].[C:69]([C:73]1[CH:78]=[CH:77][C:76]([C@@H:79]([NH3+:81])[CH3:80])=[CH:75][CH:74]=1)([CH3:72])([CH3:71])[CH3:70]>CN(C=O)C>[C:69]([C:73]1[CH:74]=[CH:75][C:76]([C@@H:79]([NH:81][C:30]([C:26]2[CH:25]=[C:24]3[C:29](=[CH:28][CH:27]=2)[N:21]([CH2:20][C:17]2[CH:16]=[CH:15][C:14]([C:9]4[C:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[CH:13][CH:12]=[CH:11][CH:10]=4)=[CH:19][CH:18]=2)[C:22]([CH3:34])=[C:23]3[CH3:33])=[O:31])[CH3:80])=[CH:77][CH:78]=1)([CH3:72])([CH3:70])[CH3:71]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 710746641-((2'-(tert-Butoxycarbonyl)biphenyl-4-yl)methyl)-2,3-dimethyl-1H-indole-5-carboxylic acidHCID 86674539(S)-1-(4-(tert-butyl)phenyl)ethanaminium chloride

Product 1

HCID 71075081(S)-tert-butyl 4'-((5-((1-(4-(tert-butyl)phenyl)ethyl)carbamoyl)-2,3-dimethyl-1H-indol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylateYield 88.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 1-((2′-(tert-butoxycarbonyl)biphenyl-4-yl)methyl)-2,3-dimethyl-1H-indole-5-carboxylic acid (100 mg) in DMF (2 mL) was added DIEA (116 μL) and HATU (88 mg). The mixture was stirred for 5 min, and then (S)-1-(4-(tert-butyl)phenyl)ethanaminium chloride (49 mg) was added. The reaction mixture was stirred at rt for 30 min. The completion of the reaction was monitored by anal. HPLC. The solvent was removed in vacuo to obtain the crude which was purified by flash chromatography (AcOEt/Hex 10→100%) to obtain the title compound (120 mg). ESI-MS (m/z): 559 [M+H-tBu]+, 615 [M+H]+, 637 [M+Na]+

Workup

  1. stirringThe reaction mixture was stirred at rt for 30 min
  2. customThe solvent was removed in vacuo
  3. customto obtain the crude which
  4. customwas purified by flash chromatography (AcOEt/Hex 10→100%)

Sources & evidence

ORD record
ord-e96fd49e0a4f4a3fb95ebc6f327ed92f
Source dataset
uspto-grants-2015_02
Patent number
US08957093B2

Reaction notes

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