Triethylamine → (E)-3-((7-chloro-3-(3-morpholino-3-oxoprop-1-enyl)imidazo[1,2-a]pyridin-2-yl)methyl)-1-cyclopropyl-1H-imidazo[4,5-c]pyridin-2(3H)-one

HRID 80634

Reaktionsgleichung

Reaktionsgleichung von HRID 80634
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8](I)=[C:9]([CH2:11][N:12]3[C:16]4[CH:17]=[N:18][CH:19]=[CH:20][C:15]=4[N:14]([CH:21]4[CH2:23][CH2:22]4)[C:13]3=[O:24])[N:10]=[C:4]2[CH:3]=1.ClC1C=CN=C(N)C=1.CCN(CC)CC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O:60]1[CH2:65][CH2:64][N:63]([C:66](=[O:69])[CH:67]=[CH2:68])[CH2:62][CH2:61]1>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8](/[CH:68]=[CH:67]/[C:66]([N:63]3[CH2:64][CH2:65][O:60][CH2:61][CH2:62]3)=[O:69])=[C:9]([CH2:11][N:12]3[C:16]4[CH:17]=[N:18][CH:19]=[CH:20][C:15]=4[N:14]([CH:21]4[CH2:23][CH2:22]4)[C:13]3=[O:24])[N:10]=[C:4]2[CH:3]=1

Komponenten

8

Edukt 5

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 98723AcryloylmorpholineHCID 5818662-Amino-4-chloropyridineHCID 679876583-((7-chloro-3-iodoimidazo[1,2-a]pyridin-2-yl)methyl)-1-cyclopropyl-1H-imidazo[4,5-c]pyridin-2(3H)-one

Produkt 1

HCID 57410366(E)-3-((7-chloro-3-(3-morpholino-3-oxoprop-1-enyl)imidazo[1,2-a]pyridin-2-yl)methyl)-1-cyclopropyl-1H-imidazo[4,5-c]pyridin-2(3H)-oneAusbeute 92 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of 3-((7-chloro-3-iodoimidazo[1,2-a]pyridin-2-yl)methyl)-1-cyclopropyl-1H-imidazo[4,5-c]pyridin-2(3H)-one 12-a (prepared following the 3-step synthesis used for 7-b, using 4-chloro-2-aminopyridine instead of 2-aminopyridine in step 1) and Et3N (2.218 mL, 8 eq) in DMF (30 mL) was degassed with nitrogen for fifteen minutes. Then palladium acetate (45 mg, 0.1 eq), triphenylphosphine (173 mg, 0.33 eq) and 1-morpholinoprop-2-en-1-one (2.516 mL, 10 eq) were added and stirring in a closed vessel was allowed at 80° C. during two hours. After cooling the mixture was quenched with ice water. After one hour stirring the precipitate was filtered off and dried in vacuo. The solid was purified over silica with dichloromethane/methanol-NH3 98/2 as eluent to provide the target compound P24 in 92% yield (884 mg). m/z=479 (M+H)+;

Aufarbeitung

  1. customthe 3-step synthesis
  2. customwas degassed with nitrogen for fifteen minutes
  3. temperatureAfter cooling the mixture
  4. customwas quenched with ice water
  5. stirringAfter one hour stirring the precipitate
  6. filtrationwas filtered off
  7. customdried in vacuo
  8. customThe solid was purified over silica with dichloromethane/methanol-NH3 98/2 as eluent
  9. customto provide the target compound P24 in 92% yield (884 mg)

Quellen und Nachweise

ORD-Eintrag
ord-0819504441b64db8a15f38ec8030cda9
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846672B2

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