1,2-Dichloroethane → 3-Hydroxy-4-{2-[(morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionylamino}-azepane-1-carboxylic acid benzyl ester

HRID 460407Notes

Reaction equation

HRID 460407 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:17][CH2:16][CH2:15][CH:14]([NH2:18])[CH:13]([OH:19])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:20]1([C:26]([NH:28][CH:29]([CH2:33][S:34]([CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)(=[O:36])=[O:35])[C:30](O)=[O:31])=[O:27])[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>ClCCl>[CH2:1]([O:8][C:9]([N:11]1[CH2:17][CH2:16][CH2:15][CH:14]([NH:18][C:30](=[O:31])[CH:29]([NH:28][C:26]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)=[O:27])[CH2:33][S:34]([CH2:37][C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)(=[O:35])=[O:36])[CH:13]([OH:19])[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 10659264Benzyl 4-amino-3-hydroxyazepane-1-carboxylateHCID 112797342-[(Morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionic acid

Product 1

HCID 694406053-Hydroxy-4-{2-[(morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionylamino}-azepane-1-carboxylic acid benzyl esterYield 93.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Crude 4-amino-3-hydroxy-azepane-1-carboxylic acid benzyl ester (150 mg, 0.57 mmol) prepared as in Reference 2, 2-[(morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionic acid (400 mg, 1.12 mmol), EDC (400 mg, 2.1 mmol), and HOBt (400 mg, 2.5 mmol) were combined. Dichloromethane (10 mL) was added followed by 4-methylmorpholine (0.5 mL). The mixture was stirred at ambient temperature for 2 hours. After dilution with ethyl acetate (100 mL) the solution was washed with 1N HCl, saturated aqueous NaHCO3 and brine, dried with MgSO4 and evaporated under vacuum. The residue was purified by flash chromatography (ethyl acetate/methanol 9: 1) to yield 3-hydroxy-4-{2-[(morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionyl-amino}-azepane-1-carboxylic acid benzyl ester (320 mg).

Workup

  1. washAfter dilution with ethyl acetate (100 mL) the solution was washed with 1N HCl, saturated aqueous NaHCO3 and brine
  2. dry with materialdried with MgSO4
  3. customevaporated under vacuum
  4. customThe residue was purified by flash chromatography (ethyl acetate/methanol 9: 1)

Sources & evidence

ORD record
ord-ca486b1ddb1f4a6984b10ae86696abab
Source dataset
uspto-grants-2007_03
Patent number
US07196099B2

Reaction notes

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