1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-Boc-S-trityl-cysteinyl-3-aminomethyl-3'-tert-butoxycarbonylbiphenyl

HRID 1739151Notes

Reaction equation

HRID 1739151 reaction equation
N([C:4]1[CH:5]=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:11]=2)[CH:7]=[CH:8][CH:9]=1)=[N+]=[N-].[C:23]([NH:30][C@H:31]([C:53]([OH:55])=O)[CH2:32][S:33][C:34]([C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24].C[CH2:57][N:58]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CO.[Pd]>[C:23]([NH:30][C@H:31]([C:53]([C:5]1[C:4]([CH2:57][NH2:58])=[CH:9][CH:8]=[CH:7][C:6]=1[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:11]=1)=[O:55])[CH2:32][S:33][C:34]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)([C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 11167161N-((1,1-Dimethylethoxy)carbonyl)-S-(triphenylmethyl)-L-cysteineHCID 195916263-Azido-3'-tert-butoxycarbonylbiphenyl

Product 1

HCID 18392929N-Boc-S-trityl-cysteinyl-3-aminomethyl-3'-tert-butoxycarbonylbiphenylYield 44%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Compound 20 (0.75 g, 2.43 mmol) was dissolved in 30 mL of methanol. A catalytic amount of 5% palladium on barium sulfate (0.30 g) was added. The mixture was hydrogenated at 1 atm for 5 hr. The catalyst was removed by filtration and the methanol was evaporated. This residue was dissolved in 40 mL of methylene chloride. N-Boc-S-trityl cysteine (1.12 g, 2.43 mmol) was added at 0° C. followed by EDCI (1 eq) and HOBT (1 eq). The mixture was stirred for 24 hr. After workup and evaporation of solvents, the residue was purified by flash column chromatography (hexane:ethyl acetate=3.2:1) to give 21 (570 mg, 44%). m.p. 84-86° C. 1H NMR (CDCl3) δ 8.17 (s, 1H), 7.95 (d, 7.7 Hz, 1H), 7.70 (d, 7.7 Hz, 1H), 7.50-7.30 (m, 9H), 7.30-7.10 (m, 11H), 6.44 (br, 1H), 4.86 (br, 1H), 4.45 (d, 4.0 Hz, 2H, CH2Ph), 3.87 (br, 1H, Cys α H), 2.75 (dd, 7.2 and 12.8 Hz, 1H, CH2S), 2.55 (dd, 5.3 and 12.8 Hz, 1H, CH2S), 1.62 (s, 9H), 1.36 (s, 9H). Anal. (C45H48N2O5S) C, H, N, S.

Workup

  1. customThe catalyst was removed by filtration
  2. customthe methanol was evaporated
  3. dissolutionThis residue was dissolved in 40 mL of methylene chloride
  4. customAfter workup and evaporation of solvents
  5. customthe residue was purified by flash column chromatography (hexane:ethyl acetate=3.2:1)

Sources & evidence

ORD record
ord-60e052ad0e8f40a9b59795cbb6af2d23
Source dataset
uspto-grants-1999_10
Patent number
US05965539

Reaction notes

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