1-Hydroxybenzotriazole → benzyl (S)-4-[2-[3-methoxy-4-[N'-(2-bromophenyl)ureido]phenylacetylamino]-1-propoxy]benzoate

HRID 354508Notes

Reaction equation

HRID 354508 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:23])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([OH:20])=O)=[CH:13][C:12]=1[O:21][CH3:22].[NH2:24][C@@H:25]([CH3:44])[CH2:26][O:27][C:28]1[CH:43]=[CH:42][C:31]([C:32]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[O:33])=[CH:30][CH:29]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C1C=CN=CC=1)C.CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:23])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([NH:24][C@@H:25]([CH3:44])[CH2:26][O:27][C:28]2[CH:43]=[CH:42][C:31]([C:32]([O:34][CH2:35][C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)=[O:33])=[CH:30][CH:29]=2)=[O:20])=[CH:13][C:12]=1[O:21][CH3:22]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23512062HCID 23512062, compoundHCID 86587801benzyl (S)-4-(2-amino-1-propoxy)benzoate

Product 1

HCID 86587802benzyl (S)-4-[2-[3-methoxy-4-[N'-(2-bromophenyl)ureido]phenylacetylamino]-1-propoxy]benzoateYield 58%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-[N′-(2-bromophenyl)ureido]-3-methoxyphenylacetic acid (480 mg, 1.27 mmol), benzyl (S)-4-(2-amino-1-propoxy)benzoate (361 mg, 1.27 mmol), EDC.HCl (364 mg, 1.90 mmol), HOBt (256 mg, 1.89 mmol) and DMAP (31 mg, 0.25 mmol) in DMF (8 ml) was stirred at room temperature overnight. The mixture was diluted with EtOAc, washed with 0.5 N HCl, brine, dried over Na2SO4 and evaporated. The residue was purified by column chromatography on silica-gel with CHCl3 to 5% MeOH in CHCl3 as eluent to give benzyl (S)-4-[2-[4-[N′-(2-bromophenyl)ureido]-3-methoxyphenylacetamido]-1-propoxy]benzoate (476 mg, 58%) as a brown solid. 1H-NMR (CDCl3) δ1.25-1.28 (m, 3 H), 3.51 (s, 2 H), 3.74 (s, 3 H), 3.95-3.97 (m, 2 H), 4.36-4.39 (m, 1 H), 5.33 (s, 2 H), 6.75-6.94 (, 5 H), 7.26-7.70 (m, 8 H), 7.99-8.26 (m, 5 H).

Workup

  1. washwashed with 0.5 N HCl, brine
  2. dry with materialdried over Na2SO4
  3. customevaporated
  4. customThe residue was purified by column chromatography on silica-gel with CHCl3 to 5% MeOH in CHCl3 as eluent

Sources & evidence

ORD record
ord-54cfe48e33574ed4991eb081be09d805
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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