Toluene → methyl 5-({[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]carbonyl}amino)nicotinate

HRID 732706Notes

Reaction equation

HRID 732706 reaction equation
C1(C)C=CC=CC=1.N(C([C:13]1[CH:14]=[N:15][CH:16]=[C:17]([CH:22]=1)[C:18]([O:20][CH3:21])=[O:19])=O)=[N+]=[N-].[C:23]1([C@H:33]([N:35]([CH2:43][C@@H:44]2[C@@H:48]([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[CH2:47][NH:46][CH2:45]2)[C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH3:34])[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1.C([N:57]([CH2:60]C)CC)C.C(OCC)(=[O:64])C>C1(C)C=CC=CC=1.CN(C=O)C>[C:38]([O:37][C:36]([N:35]([CH2:43][C@@H:44]1[C@@H:48]([C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=2)[CH2:47][N:46]([C:60]([NH:57][C:13]2[CH:14]=[N:15][CH:16]=[C:17]([CH:22]=2)[C:18]([O:20][CH3:21])=[O:19])=[O:64])[CH2:45]1)[C@@H:33]([C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1)[CH3:34])=[O:42])([CH3:40])([CH3:41])[CH3:39]

Participants

7

Reactant 5

HCID 1140TolueneHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 86628525tert-butyl [(1R)-1-(1-naphthyl)ethyl]{[(3R,4S)-4-phenylpyrrolidin-3-yl]methyl}carbamateHCID 86628561Methyl 5-(azidocarbonyl)nicotinate

Product 1

HCID 68911580methyl 5-({[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]carbonyl}amino)nicotinate

Reagents, catalysts & solvents 1

HCID 21735183Dimethylformamide tolueneSolvent

Conditions

Temperature
90 °C

Procedure

A 2 ml toluene solution of 115 mg of methyl 5-(azidocarbonyl)nicotinate was stirred with heating at 90° C. for 1Hour, and then the reaction solution was cooled down to room temperature. A mixture of 215 mg of tert-butyl [(1R)-1-(1-naphthyl)ethyl]{[(3R,4S)-4-phenylpyrrolidin-3-yl]methyl}carbamate, 0.07 ml of triethylamine and 2.0 ml of toluene/DMF (1:1) mixed solvent was added dropwise thereto and stirred at room temperature for 4Hours. The reaction solution was mixed with ethyl acetate, washed with water and saturated brine in that order and then dried with anhydrous sodium sulfate. This was concentrated under a reduced pressure, and the thus obtained residue was purified by a silica gel column chromatography (chloroform-methanol) to obtain 88 mg of methyl 5-({[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]carbonyl}amino)nicotinate as a brown oily substance.

Workup

  1. temperaturethe reaction solution was cooled down to room temperature
  2. additionmixed solvent
  3. additionwas added dropwise
  4. washwashed with water and saturated brine in that order
  5. dry with materialdried with anhydrous sodium sulfate
  6. concentrationThis was concentrated under a reduced pressure
  7. customthe thus obtained residue was purified by a silica gel column chromatography (chloroform-methanol)

Sources & evidence

ORD record
ord-fcaef4343dc54b0e8b3f9447d1a23494
Source dataset
uspto-grants-2009_09
Patent number
US07585886B2

Reaction notes

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