Pyrrolidine → 6,6-Dimethyl-2-{6-[(6-(pyrrolidin-1-yl)pyridin-2-yl)oxy]-2,3-dihydro-4h-1,4-benzoxazin-4-yl}-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-one

HRID 885988

Reaktionsgleichung

Reaktionsgleichung von HRID 885988
Br[C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]3[O:17][CH2:16][CH2:15][N:14]([C:18]4[S:19][C:20]5[C:21](=[O:29])[NH:22][C:23]([CH3:28])([CH3:27])[CH2:24][C:25]=5[N:26]=4)[C:13]=3[CH:30]=2)[CH:5]=[CH:4][CH:3]=1.[NH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.[Cl-].[Cl-].[Fe+2].[Pd+2]>[CH3:27][C:23]1([CH3:28])[NH:22][C:21](=[O:29])[C:20]2[S:19][C:18]([N:14]3[C:13]4[CH:30]=[C:9]([O:8][C:6]5[CH:5]=[CH:4][CH:3]=[C:2]([N:31]6[CH2:35][CH2:34][CH2:33][CH2:32]6)[N:7]=5)[CH:10]=[CH:11][C:12]=4[O:17][CH2:16][CH2:15]3)=[N:26][C:25]=2[CH2:24]1

Komponenten

6

Edukt 3

HCID 31268PyrrolidineHCID 23676156Sodium t-butoxideHCID 873022572-{6-[(6-Bromopyridin-2-yl)oxy]-2,3-dihydro-4h-1,4-benzoxazin-4-yl}-6,6-dimethyl-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-one

Produkt 1

HCID 685970836,6-Dimethyl-2-{6-[(6-(pyrrolidin-1-yl)pyridin-2-yl)oxy]-2,3-dihydro-4h-1,4-benzoxazin-4-yl}-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-oneAusbeute 35 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 53384307Dichloro[1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II)KatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

To a suspension of Example 382 (50 mg, 0.103 mmol) in toluene (4 mL) was added pyrrolidine (0.025 ml, 0.308 mmol), sodium tert-butoxide (20 mg, 0.206 mmol) and [1,1′-bis(di-tert-butylphosphino)ferrocene]palladium(II) dichloride (10 mg, 20% wt). The reaction was heated to 140° C. under microwave irradiation for 90 minutes then cooled to room temperature. The mixture was partitioned between DCM (50 mL) and water (50 mL); the organic phase was washed with brine (50 mL), dried (MgSO4), and concentrated in vacuo. The residue was purified by preparative HPLC (Method 6) to give the title compound (17 mg, 35%) as an off-white solid. δH (CDCl3) 7.91 (1H, d, J 2.4 Hz), 7.39 (1H, t, J 7.9 Hz), 6.93 (1H, d, J 8.9 Hz), 6.88 (1H, dd, J 8.9 and 2.4 Hz), 6.02 (1H, d, J 8.1 Hz), 5.91 (1H, d, J 7.7 Hz), 5.29 (1H, s), 4.38-4.29 (2H, m), 4.15-4.06 (2H, m), 3.45-3.37 (4H, m), 2.85 (2H, s), 2.01-1.92 (4H, m), 1.37 (6H, s). LCMS (ES+) 478.0 (M+H)+, RT 3.96 minutes (Method 1).

Aufarbeitung

  1. temperaturethen cooled to room temperature
  2. customThe mixture was partitioned between DCM (50 mL) and water (50 mL)
  3. washthe organic phase was washed with brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC (Method 6)

Quellen und Nachweise

ORD-Eintrag
ord-844457968e2547dfba3990918931a85f
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08242116B2

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