Diisopropylethylamine → 1-{3-tert-Butyl-1'-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1'H-[1,4']bipyrazolyl-5-yl}-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea

HRID 1402470Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1402470
[CH3:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[N:12]2[CH:13]=[C:14]([O:17][C@H:18]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[C@@H:21]([NH2:28])[CH2:20][CH2:19]3)[CH:15]=[CH:16][C:11]2=[N:10][N:9]=1.ClC(Cl)(Cl)C[O:32][C:33](=O)[NH:34][C:35]1[N:39]([C:40]2[CH:41]=[N:42][N:43]([CH2:45][CH2:46][O:47][CH:48]3[CH2:53][CH2:52][CH2:51][CH2:50][O:49]3)[CH:44]=2)[N:38]=[C:37]([C:54]([CH3:57])([CH3:56])[CH3:55])[CH:36]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[C:54]([C:37]1[CH:36]=[C:35]([NH:34][C:33]([NH:28][C@@H:21]2[C:22]3[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=3)[C@H:18]([O:17][C:14]3[CH:15]=[CH:16][C:11]4[N:12]([C:8]([N:3]5[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]5[CH3:1])=[N:9][N:10]=4)[CH:13]=3)[CH2:19][CH2:20]2)=[O:32])[N:39]([C:40]2[CH:41]=[N:42][N:43]([CH2:45][CH2:46][O:47][CH:48]3[CH2:53][CH2:52][CH2:51][CH2:50][O:49]3)[CH:44]=2)[N:38]=1)([CH3:57])([CH3:55])[CH3:56]

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 86687106(1S,4R)-4-[3-((S)-2-Methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamineHCID 86687175{3-tert-Butyl-1'-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1'H-[1,4']bipyrazolyl-5-yl}-carbamic acid 2,2,2-trichloro-ethyl ester

Produkt 1

HCID 866873231-{3-tert-Butyl-1'-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1'H-[1,4']bipyrazolyl-5-yl}-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureaAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of Intermediate 81d (240 mg, 0.64 mmol), Intermediate 108b (325 mg, 0.64 mmol) and DIPEA (221 μL, 1.27 mmol) in dioxane (6 mL) was stirred at 80° C. overnight. After cooling, the reaction mixture was partitioned between water and EtOAc. The aqueous phase was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by FCC on silica, using a gradient of 0-10% MeOH in DCM to afford the title compound (377 mg, 80%). LCMS (Method 4): Rt 3.48 min, m/z 737 [MH+].

Aufarbeitung

  1. temperatureAfter cooling
  2. customthe reaction mixture was partitioned between water and EtOAc
  3. extractionThe aqueous phase was extracted with EtOAc (×3)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by FCC on silica

Quellen und Nachweise

ORD-Eintrag
ord-6730cfeacea74298aa0af2d8683955b3
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08907094B2

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