1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl [(3R)-1-(cyclopentylmethyl)-3-pyrrolidinyl](5-{(1E)-3-oxo-3-[(tetrahydro-2H-pyran-2-yloxy)amino]-1-propen-1-yl)-2-pyridinyl)carbamate

HRID 2376061Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2376061
[C:1]([O:5][C:6]([N:8]([C@@H:20]1[CH2:24][CH2:23][N:22]([CH2:25][CH:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)[CH2:21]1)[C:9]1[N:14]=[CH:13][C:12](/[CH:15]=[CH:16]/[C:17](O)=[O:18])=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH:32]1[O:37][NH2:38].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C>[CH:26]1([CH2:25][N:22]2[CH2:23][CH2:24][C@@H:20]([N:8]([C:9]3[CH:10]=[CH:11][C:12](/[CH:15]=[CH:16]/[C:17](=[O:18])[NH:38][O:37][CH:32]4[CH2:33][CH2:34][CH2:35][CH2:36][O:31]4)=[CH:13][N:14]=3)[C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:21]2)[CH2:30][CH2:29][CH2:28][CH2:27]1

Komponenten

6

Edukt 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 68959166(2E)-3-(6-{(tert-butoxycarbonyl)[(3R)-1-(cyclopentylmethyl)-3-pyrrolidinyl]amino}-3-pyridinyl)acrylic acid

Produkt 1

HCID 86603680tert-butyl [(3R)-1-(cyclopentylmethyl)-3-pyrrolidinyl](5-{(1E)-3-oxo-3-[(tetrahydro-2H-pyran-2-yloxy)amino]-1-propen-1-yl)-2-pyridinyl)carbamateAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A mixture of (2E)-3-(6-{(tert-butoxycarbonyl)[(3R)-1-(cyclopentylmethyl)-3-pyrrolidinyl]amino}-3-pyridinyl)acrylic acid, O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (77 mg, 0.66 mmol), HOBt (89 mg, 0.66 mmol) and EDCI (126 mg, 0.66 mmol) in DMF (4.5 mL) was stirred at 0° C. for 1 hr and the mixture was stirred at ambient temperature for 18 hrs. The reaction mixture was evaporated in vacuo and the residue was partitioned between saturated sodium bicarbonate solution and EtOAc. The organic layer was separated, evaporated in vacuo. The residue was purified by preparative thin layer chromatography (chloroform-MeOH=10-1) to give tert-butyl [(3R)-1-(cyclopentylmethyl)-3-pyrrolidinyl](5-{(1E)-3-oxo-3-[(tetrahydro-2H-pyran-2-yloxy)amino]-1-propen-1-yl}-2-pyridinyl)carbamate (181 mg, 69%) as an amorphous powder.

Aufarbeitung

  1. stirringthe mixture was stirred at ambient temperature for 18 hrs
  2. customThe reaction mixture was evaporated in vacuo
  3. customthe residue was partitioned between saturated sodium bicarbonate solution and EtOAc
  4. customThe organic layer was separated
  5. customevaporated in vacuo
  6. customThe residue was purified by preparative thin layer chromatography (chloroform-MeOH=10-1)

Quellen und Nachweise

ORD-Eintrag
ord-7e44db7208cb45a5974b5e01c8117b44
Quelldatensatz
uspto-grants-2008_12
Patentnummer
US07465731B2

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