Nitrogen → 3-(1-tert-Butyl-1,2,3,6-tetrahydropyridin-4-yl)-7-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-amine

HRID 911988Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 911988
N#N.[Cl:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[C:6]([Cl:11])[C:5]=1[C@H:12]([O:14][C:15]1[C:16]2[O:24][CH:23]=[C:22](Br)[C:17]=2[CH:18]=[N:19][C:20]=1[NH2:21])[CH3:13].[C:26]([N:30]1[CH2:35][CH:34]=[C:33]([Sn](C)(C)C)[CH2:32][CH2:31]1)([CH3:29])([CH3:28])[CH3:27].CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1>C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CO.C(N(CC)CC)C.CN(C=O)C>[C:26]([N:30]1[CH2:31][CH:32]=[C:33]([C:22]2[C:17]3[CH:18]=[N:19][C:20]([NH2:21])=[C:15]([O:14][C@@H:12]([C:5]4[C:6]([Cl:11])=[CH:7][CH:8]=[C:9]([F:10])[C:4]=4[Cl:3])[CH3:13])[C:16]=3[O:24][CH:23]=2)[CH2:34][CH2:35]1)([CH3:29])([CH3:28])[CH3:27]

Komponenten

10

Edukt 4

HCID 947NitrogenHCID 80271Tri-o-tolylphosphineHCID 226481771-Tert-butyl-4-(trimethylstannyl)-1,2,3,6-tetrahydropyridineHCID 578127253-Bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamine

Produkt 1

HCID 578125743-(1-tert-Butyl-1,2,3,6-tetrahydropyridin-4-yl)-7-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-amine

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
115 °C

Versuchsvorschrift

In a two necked RB flask (50 mL), equipped with a N2 in let, a water condenser, and a magnetic stirrer, were placed 7-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-3-bromofuro[3,2-c]pyridine-6-amine (230 mg, 0.55 mmol), 1-tert-Butyl-1,2,3,6-tetrahydro-4-(trimethylstannyl)pyridine (240 mg, 0.79 mmol), tris(dibenzylideneacetone)dipalladium(0) (100 mg), tri-O-tolylphosphine (26 mg), DMF (10 mL) and triethylamine (1.0 mL). This reaction mixture was heated at 114-116° C. for 4 h. The TLC (10% MeOH in DCM) indicated that the starting material was consumed. From the reaction mixture DMF was removed under reduced pressure, water was added to the residue, and the mixture was extracted with DCM. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude material was purified on silica gel column chromatography eluting with 2-5% methanol in dichloromethane to give the title compound. 1H NMR (CDCl3, 300 MHz): δ=1.19 (s, 9H), 1.81 (d, J=6.6 Hz, 3H), 2.42 (br, m, 2H), 2.80 (m, 2H), 3.40 (br, m, 2H), 4.75 (br, 2H), 6.22 (br, 1H), 6.50 (m, 1H), 7.05 (t, J=8.4 Hz, 1H), 7.25 (m, J=8.4 Hz, 1H), 7.34 (s, 1H), 8.23 (s, 1H). EI-MS 478/480 (MH+).

Aufarbeitung

  1. customa water condenser, and a magnetic stirrer, were placed
  2. customwas consumed
  3. customFrom the reaction mixture DMF was removed under reduced pressure, water
  4. additionwas added to the residue
  5. extractionthe mixture was extracted with DCM
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified on silica gel column chromatography
  10. washeluting with 2-5% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-11c62c2dcd68498e8c9d108a17399930
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08022206B2

Notizen zur Reaktion

Wird geladen…