1-Hydroxybenzotriazole → HCID 19094385, compound

HRID 466232Notes

Reaction equation

HRID 466232 reaction equation
[CH3:1][O:2][P:3]([CH2:7][NH:8][CH:9]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:21][CH:20]=1)[C:10]([NH:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16])=[O:11])([O:5][CH3:6])=[O:4].[CH2:31]([O:38][C:39]([NH:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46]O)=[O:40])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[CH3:1][O:2][P:3]([CH2:7][NH:8][CH:9]([CH2:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:23][CH:24]=1)[C:10]([NH:12][CH2:13][CH2:14][C:15]([O:17][CH2:46][CH2:45][CH2:44][CH2:43][CH2:42][NH:41][C:39]([O:38][CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)=[O:40])=[O:16])=[O:11])([O:5][CH3:6])=[O:4]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 4072414Benzyl N-(5-hydroxypentyl)carbamateHCID 76083370HCID 76083370, compound

Product 1

HCID 19094385HCID 19094385, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

The compound of example 12(g) is prepared as follows: N-[2-(dimethylphosphonomethylamino)-3-(4-biphenylyl)-propionyl]-3-aminopropionic acid (700 mg; 1.61 mmol) in dimethyl formamide (DMF) (10 ml) is treated sequentially with N-benzyloxycarbonyl-5-aminopentanol (400 mg; 1.98 mmol) in DMF (2 ml), 1-hydroxybenzotriazole (HOBT) (265 mg; 1.96 mmol), 4-N,N-dimethylaminopyridine (DMAP) (239 mg; 1.96 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) (553 mg; 3.22 mmol). The mixture is stirred for 20 hours, then partitioned between ethyl acetate (50 ml) and 1N HCl(30 ml). The organic layer is washed with a saturated solution of sodium bicarbonate (30 ml), then with brine (30 ml) before being dried over anhydrous sodium sulfate. After concentration under reduced pressure, the oily residue is purified by column chromatography on silica gel, eluting first with ethyl acetate, then with 5% methanol in methylene chloride to yield N-benzyloxycarbonyl-5-aminopentyl N-[2-(dimethylphosphonomethyl amino)-3-(4-biphenylyl)-propionyl]-3-aminopropionate as an oil; Rf(SiO2 ; MeOH/CH2Cl2):0.4.

Workup

  1. custompartitioned between ethyl acetate (50 ml) and 1N HCl(30 ml)
  2. washThe organic layer is washed with a saturated solution of sodium bicarbonate (30 ml)
  3. dry with materialwith brine (30 ml) before being dried over anhydrous sodium sulfate
  4. concentrationAfter concentration under reduced pressure
  5. customthe oily residue is purified by column chromatography on silica gel
  6. washeluting first with ethyl acetate

Sources & evidence

ORD record
ord-0e607a9af4414bfaa4ea3ad8b58b14fc
Source dataset
uspto-grants-1992_10
Patent number
US05155100

Reaction notes

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