Triethylamine → N-[(3S*,4S*)-4-(3-Benzyl-1-cyclopropyl-ureidomethyl)-pyrrolidin-3-ylmethyl]-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide

HRID 1158432Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1158432
C(OC([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([CH2:34][N:35]([CH:46]2[CH2:48][CH2:47]2)[C:36]([NH:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[O:37])[CH2:9]1)=O)(C)(C)C.C(OC(N1C[C@@H](CN(C(C)C)C(=O)C2C=CC(OC)=C(OCCCOC)C=2)[C@H](CNC2CC2)C1)=O)(C)(C)C.C(N(CC)CC)C.C(N=C=O)C1C=CC=CC=1>C1COCC1.O>[CH2:39]([NH:38][C:36](=[O:37])[N:35]([CH2:34][C@@H:10]1[CH2:9][NH:8][CH2:12][C@H:11]1[CH2:13][N:14]([CH:31]([CH3:32])[CH3:33])[C:15](=[O:30])[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=1)[CH:46]1[CH2:47][CH2:48]1)[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 76639Benzyl isocyanateHCID 68616408(3R*,4R*)-3-Cyclopropylaminomethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 68616937(3R*,4R*)-3-(3-Benzyl-1-cyclopropyl-ureidomethyl)-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 59512259N-[(3S*,4S*)-4-(3-Benzyl-1-cyclopropyl-ureidomethyl)-pyrrolidin-3-ylmethyl]-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

(3R*,4R*)-3-(3-Benzyl-1-cyclopropyl-ureidomethyl)-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl Ester To a solution of ((3R*,4R*)-3-cyclopropylaminomethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (235 mg, 0.440 mmol) in THF (6 mL) is added triethylamine (123 μL, 0.880 mmol) followed by benzylisocyanate (54 μL, 0.440 mmol). The mixture is stirred at RT for 2 h before water is added. Extraction with ethyl acetate, drying of the combined extracts (Na2SO4), filtration and evaporation of the solvent affords the crude product which is purified by flash chromatography on silica gel (eluent gradient: CH2Cl2 100% to CH2Cl2/MeOH 9:1) to give the title compound. MS (LC-MS): 667.1M+H]+; tR (HPLC, Macherey-Nagel Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 ml/min): 6.26 min.

Aufarbeitung

  1. additionis added
  2. extractionExtraction with ethyl acetate
  3. dry with materialdrying of the combined extracts (Na2SO4), filtration and evaporation of the solvent
  4. customaffords the crude product which
  5. customis purified by flash chromatography on silica gel (eluent gradient: CH2Cl2 100% to CH2Cl2/MeOH 9:1)

Quellen und Nachweise

ORD-Eintrag
ord-88bfeeca94554769b8f5c11deacc0b2f
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07807709B2

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