4-Methylmorpholine → N-benzyloxy-2(R)-[(3,4-methylendioxybenzyl)-(2,6-dimethyl-4-methoxybenzenesulfonyl)amino]-3-[(2-pyrrol-1-yl)phenylcarbonylamino]-propionamide

HRID 2298008Notes

Reaction equation

HRID 2298008 reaction equation
[CH2:1]1[O:43][C:42]2[CH:41]=[CH:40][C:5]([CH2:6][N:7]([S:27]([C:30]3[C:35]([CH3:36])=[CH:34][C:33]([O:37][CH3:38])=[CH:32][C:31]=3[CH3:39])(=[O:29])=[O:28])[C@H:8]([CH2:12][NH:13][C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[N:22]3[CH:26]=[CH:25][CH:24]=[CH:23]3)=[O:15])[C:9](O)=[O:10])=[CH:4][C:3]=2[O:2]1.[CH2:44]([O:51][NH2:52])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C)C=O>[CH2:44]([O:51][NH:52][C:9](=[O:10])[C@H:8]([N:7]([CH2:6][C:5]1[CH:40]=[CH:41][C:42]2[O:43][CH2:1][O:2][C:3]=2[CH:4]=1)[S:27]([C:30]1[C:31]([CH3:39])=[CH:32][C:33]([O:37][CH3:38])=[CH:34][C:35]=1[CH3:36])(=[O:28])=[O:29])[CH2:12][NH:13][C:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[N:22]1[CH:23]=[CH:24][CH:25]=[CH:26]1)=[O:15])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 102313O-BenzylhydroxylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 183375482(R)-[(3,4-methylendioxybenzyl)-(2,6-dimethyl-4-methoxybenzenesulfonyl)amino]-3-[(2-pyrrol-1-yl)phenylcarbonylamino]-propionic acid

Product 1

HCID 18337565N-benzyloxy-2(R)-[(3,4-methylendioxybenzyl)-(2,6-dimethyl-4-methoxybenzenesulfonyl)amino]-3-[(2-pyrrol-1-yl)phenylcarbonylamino]-propionamideYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 2(R)-[(3,4-methylendioxybenzyl)-(2,6-dimethyl-4-methoxybenzenesulfonyl)amino]-3-[(2-pyrrol-1-yl)phenylcarbonylamino]-propionic acid (approximately 1.3 mmol), O-benzylhydroxylamine (0.6 ml, 3.9 mmol) and 1-hydroxybenzotriazole hydrate (199 mg, 1.3 mmol), and N-methylmorpholine (0.44 ml, 3.9 mmol) in anhydrous dimethylformamide (20 ml) was added 1-ethyl-3(3-dimethylamino)-propyl carbodiimide hydrochloride salt (375 mg, 1.95 mmol). The mixture was stirred overnight and then condensed on the roto-evaporator. The remainder was taken up in ethyl acetate (60 ml) and partitioned with an equal volume of 1.5% aqueous hydrochloric acid. The ethyl acetate phase was collected and washed consecutively with equal volumes of 5% sodium bicarbonate and then brine. The aqueous phases were back extracted with ethyl acetate (2×60 ml) and the organic layers combined, dried with magnesium sulfate, filtered and condensed. The residue was purified by preparative TLC (2% methanol-methylene chloride) providing N-benzyloxy-2(R)-[(3,4-methylendioxybenzyl)-(2,6-dimethyl-4-methoxybenzenesulfonyl)amino]-3-[(2-pyrrol-1-yl)phenylcarbonylamino]-propionamide as a light yellow foamy solid (490 mg).

Workup

  1. customcondensed
  2. customon the roto-evaporator
  3. custompartitioned with an equal volume of 1.5% aqueous hydrochloric acid
  4. customThe ethyl acetate phase was collected
  5. washwashed consecutively with equal volumes of 5% sodium bicarbonate
  6. extractionThe aqueous phases were back extracted with ethyl acetate (2×60 ml)
  7. dry with materialdried with magnesium sulfate
  8. filtrationfiltered
  9. customcondensed
  10. customThe residue was purified by preparative TLC (2% methanol-methylene chloride)

Sources & evidence

ORD record
ord-5f76931865ed452292d606bb818a0c9f
Source dataset
uspto-grants-2002_12
Patent number
US06492394B1

Reaction notes

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