3-hydroxy-1,2,3-benzotriazin-4(3H)-one → methyl 3-(4-{[4-{{2-[(benzhydryloxy)carbonyl]phenyl}[(benzyloxy)(oxo)acetyl]amino}-N-(methoxycarbonyl)-L-phenylalanyl]amino}butoxy)-1-hydroxy-2-naphthoate

HRID 488683Notes

Reaction equation

HRID 488683 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[C:8]([C:18]([O:20][CH3:21])=[O:19])=[C:9]([OH:17])[C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2.[CH:22]([O:35][C:36](=[O:72])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[N:43]([C:60](=[O:71])[C:61]([O:63][CH2:64][C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1)=[O:62])[C:44]1[CH:49]=[CH:48][C:47]([CH2:50][CH:51]([C:57](O)=[O:58])[NH:52][C:53]([O:55][CH3:56])=[O:54])=[CH:46][CH:45]=1)([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.Cl.CN(C)CCCN=C=NCC.ON1C(=O)C2C=CC=CC=2N=N1>CN(C=O)C.C(N(CC)CC)C>[CH:22]([O:35][C:36]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[N:43]([C:60](=[O:71])[C:61]([O:63][CH2:64][C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1)=[O:62])[C:44]1[CH:45]=[CH:46][C:47]([CH2:50][C@@H:51]([C:57]([NH:1][CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]2[C:8]([C:18]([O:20][CH3:21])=[O:19])=[C:9]([OH:17])[C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)=[O:58])[NH:52][C:53]([O:55][CH3:56])=[O:54])=[CH:48][CH:49]=1)=[O:72])([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 730263-hydroxy-1,2,3-benzotriazin-4(3H)-oneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 222719502-{Benzyloxyoxalyl-[4-(2-carboxy-2-methoxycarbonylamino-ethyl)-phenyl]-amino}-benzoic acid benzhydryl esterHCID 22271969Methyl 3-(4-aminobutoxy)-1-hydroxy-2-naphthoate

Product 1

HCID 86585332methyl 3-(4-{[4-{{2-[(benzhydryloxy)carbonyl]phenyl}[(benzyloxy)(oxo)acetyl]amino}-N-(methoxycarbonyl)-L-phenylalanyl]amino}butoxy)-1-hydroxy-2-naphthoateYield 61%

Reagents, catalysts & solvents 2

HCID 8471TriethylamineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a mixture of methyl 3-(4-aminobutoxy)-1-hydroxy-2-naphthoate (18 mg, 0.055 mmol), 2-{benzyloxyoxalyl-[4-(2-carboxy-2-methoxycarbonylamino-ethyl)-phenyl]-amino}-benzoic acid benzhydryl ester (40 mg, 0.058 mmol), 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (13 mg, 0.068 mmol) and 3-hydroxy-1,2,3-benzotriazin-4(3H)-one (13 mg, 0.080 mmol) in DMF (0.2 mL) was added triethylamine (1 drop). The reaction was stirred at ambient temperature for 5 hours, concentrated under reduced pressure and purified on silica gel eluting with 75% ethyl acetate/hexanes to provide the titled compound (32 mg, 61%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. custompurified on silica gel eluting with 75% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-ec17fb6f62694cd9a04a0deed69d058f
Source dataset
uspto-grants-2005_12
Patent number
US06972340B2

Reaction notes

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