Triethylamine → N-BOC-S-trityl-cysteine 4-amino-2-phenylbenzoyl methionine methyl ester

HRID 1739139Notes

Reaction equation

HRID 1739139 reaction equation
[C:1]([NH:8][C@H:9]([C:31]([OH:33])=[O:32])[CH2:10][S:11][C:12]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CCN(CC)CC.C(N[C@H](C(O)=O)CSC(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)(OC(C)(C)C)=O.COC(=O)[C@H](CCSC)NC(=O)C1C=CC(N)=CC=1.[CH3:93][O:94][C:95](=[O:117])[C@H:96]([CH2:113][CH2:114][S:115][CH3:116])[NH:97][C:98](=[O:112])[C:99]1[CH:104]=[CH:103][C:102]([NH2:105])=[CH:101][C:100]=1[C:106]1[CH:111]=[CH:110][CH:109]=[CH:108][CH:107]=1>C1COCC1.C(Cl)Cl>[C:1]([NH:8][C@H:9]([C:31]([OH:33])=[O:32])[CH2:10][S:11][C:12]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:93][O:94][C:95](=[O:117])[C@H:96]([CH2:113][CH2:114][S:115][CH3:116])[NH:97][C:98](=[O:112])[C:99]1[CH:104]=[CH:103][C:102]([NH2:105])=[CH:101][C:100]=1[C:106]1[CH:107]=[CH:108][CH:109]=[CH:110][CH:111]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11167161N-((1,1-Dimethylethoxy)carbonyl)-S-(triphenylmethyl)-L-cysteineHCID 18666758N-(4-Amino-2-phenylbenzoyl)methionine methyl esterHCID 67565269N-BOC-S-trityl-cysteine 4-aminobenzoyl methionine methyl ester2×

Product 1

HCID 67565912N-BOC-S-trityl-cysteine 4-amino-2-phenylbenzoyl methionine methyl esterYield 16%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-BOC-S-trityl-cysteine (0.31 g, 0.66 mmol) in dry THF (11 ml) was reacted with Et3N (0.10 ml), IBCF (0.09 ml, 0.73 mmol) at -10° C. as described for N-BOC-S-trityl-cysteine-4-aminobenzoyl methionine methyl ester in Example 1. 4-amino-2-phenylbenzoyl methionine methyl ester (0.24 g, 0.66 mmol) in dry CH2Cl2 (3.5 ml) was added and the mixture was allowed to stir overnight under nitrogen. It was worked up as described as further described for N-BOC-S-trityl-cysteine-4-aminobenzoyl methionine methyl ester in Example 1, and after drying the crude material was chromatographed on silica gel using a 2:1 mixture of hexanes and ethyl acetate to give 84.70 mg (16.0%) of pure product. mp 100-103° C.; 1H NMR (CDCl3) 1.41 (9H,s), 1.61-1.78 (1H, m), 1.84-1.95 (1H, m), 2.00 (3H, s), 2.05 (2H, t, J=7.6 Hz), 2.63 (1H, dd, J=12.7 Hz, 6.9 Hz), 2.72 (1H, dd, J=12.7 Hz, 5.51 Hz), 3.64 (3H, s), 4.02 (1H, br s), 4.58-4.63 (1H, m), 4.90 (1H, d, J=7.4 Hz), 6.10 (1H, d, J=6.6 Hz), 7.18-7.30 (10H, m), 7.37-7.44 (11H, m), 7.50 (1H, s), 7.58 (1H, d, J=8.2 Hz), 8.69 (1H, s); 13C NMR (CDCl3) 15.21, 28.20, 29.38, 31.24, 33.00, 51.77, 52.35, 54.15, 67.30, 80.85, 118.18, 120.86, 126.88, 127.90, 128.03, 128.56, 128.66, 129.44, 129.79, 130.14, 156.00, 168.52, 169.11, 171.85.

Workup

  1. dry with materialafter drying the crude material
  2. customwas chromatographed on silica gel using
  3. additiona 2:1 mixture of hexanes and ethyl acetate

Sources & evidence

ORD record
ord-08c09fcd088d4655b015f0c00cea65cc
Source dataset
uspto-grants-1999_10
Patent number
US05965539

Reaction notes

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