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Hydrochloric Acid → N-BOC-S-trityl-cysteine 4-amino-1-naphthoyl methionine methyl ester

HRID 1739148
Notes
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Reaction equation

HRID 1739148 reaction equation
CCN(CC)CC.Cl.[CH3:9][O:10][C:11](=[O:31])[C@H:12]([CH2:27][CH2:28][S:29][CH3:30])[NH:13][C:14]([C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]([NH2:26])=[CH:18][CH:17]=1)=[O:15].[C:32]([NH:39][C@H:40]([C:62]([OH:64])=[O:63])[CH2:41][S:42][C:43]([C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33].COC(=O)[C@H](CCSC)NC(=O)C1C=CC(N)=CC=1>C1COCC1.C(Cl)Cl>[C:32]([NH:39][C@H:40]([C:62]([OH:64])=[O:63])[CH2:41][S:42][C:43]([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)([C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33].[CH3:9][O:10][C:11](=[O:31])[C@H:12]([CH2:27][CH2:28][S:29][CH3:30])[NH:13][C:14]([C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]([NH2:26])=[CH:18][CH:17]=1)=[O:15]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 537463294-Amino-1-naphthoyl methionine methyl esterHCID 67565269N-BOC-S-trityl-cysteine 4-aminobenzoyl methionine methyl ester

Product 1

HCID 67566653N-BOC-S-trityl-cysteine 4-amino-1-naphthoyl methionine methyl esterYield 37.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-BOC-S-trityl-Cys (0.31 g, 0.67 mmol) in dry THF (11.2 ml) was reacted with Et3N (0.10 ml) and IBCF (0.10 ml, 0.74 mmol) at -10° C. as described above. HCl.4-amino-1-naphthoyl methionine methyl ester (0.25 g, 0.67 mmol) in dry CH2Cl2 (3.5 ml) was added and the mixture was stirred overnight under nitrogen. The mixture was worked up as described for N-BOC-S-trityl-cysteine-4-aminobenzoyl methionine methyl ester in Example 1, and the crude material was chromatographed on silica gel using a 2:1 mixture of hexanes and ethyl acetate to give 0.20 g (37.5%) of pure product. 1H NMR (CDCl3) 1.48 (9H, s), 2.10-2.20 (4H, m), 2.30-2.37 (1H, m), 2.63 (2H, t, J=7.4), 2.74 (1H, J=12.9 Hz, J=5.3 Hz), 2.90 (1H, J=12.9 Hz, 6.2 Hz), 3.81 (3H, 9), 4.96-5.03 (2H, m), 6.77 (1H, d, J=8.0 Hz), 7.18-7.33 (11H, m), 7.44-7.56 (7H, m), 7.60 (1H, d, J=7.7 Hz), 7.88 (1H, d, J=8.0 Hz), 8.00 (1H, d, J=7.1 Hz), 8.37 (1H, d, J=8.4 Hz), 8.94 (1H, br s); 13C NMR (CDCl3) 15.23, 26.52, 31.41, 31.50, 52.98, 53.31, 56.79, 68.15, 122.52, 123.54, 126.16, 126.99, 128.03, 128.39, 129.52, 132.30, 134.04, 135.24, 168.08, 172.38, 173.94.

Workup

  1. customthe crude material was chromatographed on silica gel using
  2. additiona 2:1 mixture of hexanes and ethyl acetate

Sources & evidence

ORD record
ord-5e3d6b37ed8b48789f56de6ec3b8c475
Source dataset
uspto-grants-1999_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05965539

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes