1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (2Z)-3-(5-chloro-6-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}-3-pyridinyl)-2-fluoro-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide

HRID 226390Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 226390
CCN=C=NCCCN(C)C.[Cl:12][C:13]1[CH:14]=[C:15](/[CH:33]=[C:34](\[F:38])/[C:35](O)=[O:36])[CH:16]=[N:17][C:18]=1[NH:19][C@@H:20]1[CH2:25][CH2:24][CH2:23][N:22]([CH2:26][CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[CH2:21]1.[O:39]1[CH2:44][CH2:43][CH2:42][CH2:41][CH:40]1[O:45][NH2:46].C1C=CC2N(O)N=NC=2C=1.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[Cl:12][C:13]1[CH:14]=[C:15](/[CH:33]=[C:34](\[F:38])/[C:35]([NH:46][O:45][CH:40]2[CH2:41][CH2:42][CH2:43][CH2:44][O:39]2)=[O:36])[CH:16]=[N:17][C:18]=1[NH:19][C@@H:20]1[CH2:25][CH2:24][CH2:23][N:22]([CH2:26][CH:27]2[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]2)[CH2:21]1

Komponenten

8

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 68961945(2Z)-3-(5-chloro-6-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}-3-pyridinyl)-2-fluoroacrylic acid

Produkt 1

HCID 86603698(2Z)-3-(5-chloro-6-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}-3-pyridinyl)-2-fluoro-N-(tetrahydro-2H-pyran-2-yloxy)acrylamideAusbeute 67 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

EDCI (0.32 g) was added to the solution of (2Z)-3-(5-chloro-6-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}-3-pyridinyl)-2-fluoroacrylic acid (0.68 g), O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (0.24 g), and HOBT (0.28 g) in DMF (13.6 ml) and the mixture was stirred at ambient temperature for 20 hr. The reaction mixture was poured into a mixture of AcOEt and aq NaHCO3. The separated organic layer was washed with water, dried over magnesium sulfate and evaporated in vacuo. The residue was crystallization with solution of iPE and hexane to give (2Z)-3-(5-chloro-6-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}-3-pyridinyl)-2-fluoro-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide (0.57 g).

Aufarbeitung

  1. washThe separated organic layer was washed with water
  2. dry with materialdried over magnesium sulfate
  3. customevaporated in vacuo
  4. customcrystallization with solution of iPE and hexane

Quellen und Nachweise

ORD-Eintrag
ord-d2386f0b01164b5bb7c7cb99f938ead6
Quelldatensatz
uspto-grants-2009_07
Patentnummer
US07557127B2

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