Triphenylphosphine → N-[(4-{4-[(1-ethylpiperidin-4-yl)oxy]phenyl}tetrahydro-2H-pyran-4-yl)methyl]pyridin-2-amine

HRID 273041

Reaktionsgleichung

Reaktionsgleichung von HRID 273041
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][CH2:8][C:9]1([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1.[CH2:22]([N:24]1[CH2:29][CH2:28][CH:27](O)[CH2:26][CH2:25]1)[CH3:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[CH2:22]([N:24]1[CH2:29][CH2:28][CH:27]([O:21][C:18]2[CH:19]=[CH:20][C:15]([C:9]3([CH2:8][NH:7][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=4)[CH2:10][CH2:11][O:12][CH2:13][CH2:14]3)=[CH:16][CH:17]=2)[CH2:26][CH2:25]1)[CH3:23]

Komponenten

6

Edukt 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 770561-Ethylpiperidin-4-olHCID 685779444-{4-[(pyridin-2-ylamino)methyl]tetrahydro-2H-pyran-4-yl}phenol

Produkt 1

HCID 59837384N-[(4-{4-[(1-ethylpiperidin-4-yl)oxy]phenyl}tetrahydro-2H-pyran-4-yl)methyl]pyridin-2-amineAusbeute 23 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 4-{4-[(pyridin-2-ylamino)methyl]tetrahydro-2H-pyran-4-yl}phenol (250 mg, 0.881 mmol), 1-ethylpiperidin-4-ol (103 mg, 0.8 mmol) and triphenylphosphine (231 mg, 0.881 mmol) in THF (5 ml) at 0° C. under nitrogen was added dropwise diisopropyl azodicarboxylate (95% solution, 183 μl, 0.881 mmol). Reaction was stirred for 10 minutes then warmed to room temperature for 72 hours until complete. THF was removed in vacuo and the residue partitioned between ethyl acetate (50 ml) and saturated sodium bicarbonate solution (50 ml). The organic layer was separated, dried over sodium sulphate, filtered and concentrated in vacuo. Crude product was purified by flash chromatography eluting with dichloromethane:methanol:ammonia (100:0:0 to 96:4:0.4 by volume) to give the title compound (8.2 mg, 23%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 1.05 (t, 3H), 1.80-1.98 (m, 4H), 2.00-2.18 (m, 4H), 2.28-2.42 (m, 2H), 2.44-2.54 (q, 2H), 2.72-2.86 (m, 2H), 3.50 (d, 2H), 3.55-3.62 (m, 2H), 3.78-3.88 (m, 2H), 4.00-4.08 (m, 1H), 4.30-4.39 (m, 1H), 6.22 (d, 1H), 6.50 (t, 1H), 6.90 (d, 2H), 7.23 (d, 2H), 7.30 (t, 1H), 8.01 (d, 1H). LRMS APCI+ m/z 396 [MH]+. HRMS ESI+ m/z 396.2641 [MH]+.

Aufarbeitung

  1. customReaction
  2. customTHF was removed in vacuo
  3. customthe residue partitioned between ethyl acetate (50 ml) and saturated sodium bicarbonate solution (50 ml)
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customCrude product was purified by flash chromatography
  9. washeluting with dichloromethane:methanol:ammonia (100:0:0 to 96:4:0.4 by volume)

Quellen und Nachweise

ORD-Eintrag
ord-52dd5667299149569b348c877751ccde
Quelldatensatz
uspto-grants-2008_11
Patentnummer
US07456164B2

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