4-Methylmorpholine → tert-butyl-2(R)-[(3,4-methylendioxybenzyl)-(2,6-dimethyl-4-methoxybenzenesulfonyl)amino]-3-[(2-pyrrol-1-yl)phenylcarbonylamino]-propionate

HRID 2298006Notes

Reaction equation

HRID 2298006 reaction equation
[C:1]([O:5][C:6](=[O:34])[C@H:7]([N:10]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]2[O:31][CH2:32][O:33][C:27]=2[CH:26]=1)[S:11]([C:14]1[C:19]([CH3:20])=[CH:18][C:17]([O:21][CH3:22])=[CH:16][C:15]=1[CH3:23])(=[O:13])=[O:12])[CH2:8][NH2:9])([CH3:4])([CH3:3])[CH3:2].[C:35]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[N:44]1[CH:48]=[CH:47][CH:46]=[CH:45]1)(O)=[O:36].O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.C(N=C=N)CC>CN(C)C1C=CN=CC=1.CN(C)C=O>[C:1]([O:5][C:6](=[O:34])[C@H:7]([N:10]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]2[O:31][CH2:32][O:33][C:27]=2[CH:26]=1)[S:11]([C:14]1[C:19]([CH3:20])=[CH:18][C:17]([O:21][CH3:22])=[CH:16][C:15]=1[CH3:23])(=[O:12])=[O:13])[CH2:8][NH:9][C:35]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[N:44]1[CH:48]=[CH:47][CH:46]=[CH:45]1)=[O:36])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 7285212-(1H-pyrrol-1-yl)benzoic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 18621663Propyl carbodiimide hy-drochlorideHCID 69762296tert-butyl 2(R)-[(3,4-methylendioxybenzyl)-(2,6-dimethyl-4-methoxybenzenesulfonyl)amino]-3-amino-propionate

Product 1

HCID 69762802tert-butyl-2(R)-[(3,4-methylendioxybenzyl)-(2,6-dimethyl-4-methoxybenzenesulfonyl)amino]-3-[(2-pyrrol-1-yl)phenylcarbonylamino]-propionate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a mixture of tert-butyl-2(R)-[(3,4-methylendioxybenzyl)-(2,6-dimethyl-4-methoxybenzenesulfonyl)amino]-3-amino-propionate (1.02 g, 2.0 mmol), 1-(2-carboxyphenyl)pyrrole (581 mg, 3.1 mmol), 1-hydroxybenzotriazole hydrate (279 mg, 2.0 mmol), N-methylmorpholine (0.8 ml, 7.3 mmol) and 4-dimethylaminopyridine (30 mg, 0.25 mmol) in dry dimethylformamide (25 ml) was added 1-ethyl-3,3-dimethylamino)-propyl carbodiimide hydrochloride salt (600 mg, 3.1 mmol) and the material was stirred overnight. The dimethylformamide was removed on the rotary evaporator and the residue was taken up in ethyl acetate (80 ml) and partitioned with an equal volume of aqueous hydrochloric acid (1.5%, 80 ml). The organic phase was collected and washed with equal volumes of 5% aqueous sodium bicarbonate and then brine. The aqueous phases were back extracted with ethyl acetate (2×80 ml) and the organic phases combined, dried over magnesium sulfate, filtered and condensed to provide a residue. This material was chromatographed using preparative TLC plates (45% ethyl acetate/hexanes) to afford tert-butyl-2(R)-[(3,4-methylendioxybenzyl)-(2,6-dimethyl-4-methoxybenzenesulfonyl)amino]-3-[(2-pyrrol-1-yl)phenylcarbonylamino]-propionate) as a pale yellow foamy solid (927 mg).

Workup

  1. customThe dimethylformamide was removed on the rotary evaporator
  2. custompartitioned with an equal volume of aqueous hydrochloric acid (1.5%, 80 ml)
  3. customThe organic phase was collected
  4. washwashed with equal volumes of 5% aqueous sodium bicarbonate
  5. extractionThe aqueous phases were back extracted with ethyl acetate (2×80 ml)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customcondensed
  9. customto provide a residue
  10. customThis material was chromatographed

Sources & evidence

ORD record
ord-f746441b0c4643928836c2734e7982c7
Source dataset
uspto-grants-2002_12
Patent number
US06492394B1

Reaction notes

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