1,4-Dioxane → 1-[3-tert-Butyl-1'-(2-morpholin-4-yl-ethyl)-1'H-[1,4']bipyrazolyl-5-yl]-3-((1S,4R)-4-[3-((2S,6R)-2,6-dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl)-urea formate salt

HRID 630922Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 630922
[CH3:1][C@H:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([CH3:8])[N:3]1[C:9]1[N:13]2[CH:14]=[C:15]([O:18][C@H:19]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[C@@H:22]([NH2:29])[CH2:21][CH2:20]3)[CH:16]=[CH:17][C:12]2=[N:11][N:10]=1.ClC(Cl)(Cl)C[O:33][C:34](=[O:59])[NH:35][C:36]1[N:40]([C:41]2[CH:42]=[N:43][N:44]([CH2:46][CH2:47]OC3CCCCO3)[CH:45]=2)[N:39]=[C:38]([C:55]([CH3:58])([CH3:57])[CH3:56])[CH:37]=1.[CH3:62][CH2:63][N:64](C(C)C)[CH:65]([CH3:67])C.[O:71]1CCOCC1>>[CH:34]([OH:59])=[O:33].[C:55]([C:38]1[CH:37]=[C:36]([NH:35][C:34]([NH:29][C@@H:22]2[C:23]3[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=3)[C@H:19]([O:18][C:15]3[CH:16]=[CH:17][C:12]4[N:13]([C:9]([N:3]5[C@H:2]([CH3:1])[CH2:7][CH2:6][CH2:5][C@@H:4]5[CH3:8])=[N:10][N:11]=4)[CH:14]=3)[CH2:20][CH2:21]2)=[O:59])[N:40]([C:41]2[CH:42]=[N:43][N:44]([CH2:46][CH2:47][N:64]3[CH2:65][CH2:67][O:71][CH2:62][CH2:63]3)[CH:45]=2)[N:39]=1)([CH3:56])([CH3:57])[CH3:58]

Komponenten

5

Edukt 4

HCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 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 esterHCID 89624184(1S,4R)-4-[3-(cis-2,6-Dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

Produkt 1

HCID 866872111-[3-tert-Butyl-1'-(2-morpholin-4-yl-ethyl)-1'H-[1,4']bipyrazolyl-5-yl]-3-((1S,4R)-4-[3-((2S,6R)-2,6-dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl)-urea formate saltAusbeute 95 %

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of Intermediate 96c (200 mg, 0.51 mmol), Intermediate 108b (261 mg, 0.51 mmol) and DIPEA (178 μL, 1.02 mmol) in dioxane (5 mL) was stirred at 80° C. overnight. After cooling, the reaction mixture was partitioned between water and DCM. 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 1-10% MeOH in DCM to afford the title compound (364 mg, 95%) as a glassy white solid %). LCMS (Method 4): Rt 3.69 min, m/z 751 [MH+].

Aufarbeitung

  1. temperatureAfter cooling
  2. customthe reaction mixture was partitioned between water and DCM
  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-ef346495419842b290f751a593f02a89
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09315503B2

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