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

HRID 350568Notes

Reaction equation

HRID 350568 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) δ 1.25–1.28 (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 (m, 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-6e81687c64cc4f8fb4cc2efe6f72d5ce
Source dataset
uspto-grants-2007_02
Patent number
US07179819B2

Reaction notes

Loading…