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Diisopropylethylamine → 1-[3-(1-{[tert-Butyl(diphenyl)silyl]oxy)-2-methylpropan-2-yl)-1-{3-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]phenyl}-1H-pyrazol-5-yl]-3-[(1S,4R)-4-({3-[(2S)-2-methylpiperidin-1-yl][1,2,4]triazolo[4,3-a]pyridin-6-yl}oxy)-1,2,3,4-tetrahydronaphthalen-1-yl]urea

HRID 1402439
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1402439
ClC(Cl)(Cl)CO[C:5](=[O:50])[NH:6][C:7]1[N:8]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH2:41][CH2:42][O:43][CH:44]3[CH2:49][CH2:48][CH2:47][CH2:46][O:45]3)[CH:35]=2)[N:9]=[C:10]([C:12]([CH3:33])([CH3:32])[CH2:13][O:14][Si:15]([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:11]=1.[CH3:53][C@H:54]1[CH2:59][CH2:58][CH2:57][CH2:56][N:55]1[C:60]1[N:64]2[CH:65]=[C:66]([O:69][C@H:70]3[C:79]4[C:74](=[CH:75][CH:76]=[CH:77][CH:78]=4)[C@@H:73]([NH2:80])[CH2:72][CH2:71]3)[CH:67]=[CH:68][C:63]2=[N:62][N:61]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[Si:15]([O:14][CH2:13][C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:80][C@@H:73]2[C:74]3[C:79](=[CH:78][CH:77]=[CH:76][CH:75]=3)[C@H:70]([O:69][C:66]3[CH:67]=[CH:68][C:63]4[N:64]([C:60]([N:55]5[CH2:56][CH2:57][CH2:58][CH2:59][C@@H:54]5[CH3:53])=[N:61][N:62]=4)[CH:65]=3)[CH2:71][CH2:72]2)=[O:50])[N:8]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH2:41][CH2:42][O:43][CH:44]3[CH2:49][CH2:48][CH2:47][CH2:46][O:45]3)[CH:35]=2)[N:9]=1)([CH3:33])[CH3:32])([C:28]([CH3:29])([CH3:31])[CH3:30])([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
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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 86687287(5-[2-(tert-Butyl-diphenyl-silanyloxy)-1,1-dimethyl-ethyl]-2-{3-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester

Produkt 1

HCID 86687288
1-[3-(1-{[tert-Butyl(diphenyl)silyl]oxy)-2-methylpropan-2-yl)-1-{3-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]phenyl}-1H-pyrazol-5-yl]-3-[(1S,4R)-4-({3-[(2S)-2-methylpiperidin-1-yl][1,2,4]triazolo[4,3-a]pyridin-6-yl}oxy)-1,2,3,4-tetrahydronaphthalen-1-yl]urea
Ausbeute 73,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A solution of Intermediate 153f (377 mg, 0.48 mmol) in 1,4-dioxane (4.8 mL) was treated with Intermediate 81d (164 mg, 0.43 mmol) and DIPEA (0.095 mL, 0.54 mmol) and the mixture was stirred at 70° C. for 30 mins then at 50° C. for 64 h then at 70° C. for 22 h. The cooled solution was concentrated in vacuo, and the residue was partitioned between DCM and water. The phases were separated and the aqueous layer was extracted with DCM (×2). The combined organic phase was washed with brine, dried (Na2SO4) and concentrated in vacuo to a brown gum. The gum was purified by FCC, using 0-7% MeOH in DCM to give the title compound as a brown glass (320 mg, 72%). LCMS (Method 3): Rt 5.66 min, m/z 1017.7 [MH+].

Aufarbeitung

  1. waitat 50° C. for 64 h
  2. waitat 70° C. for 22 h
  3. concentrationThe cooled solution was concentrated in vacuo
  4. customthe residue was partitioned between DCM and water
  5. customThe phases were separated
  6. extractionthe aqueous layer was extracted with DCM (×2)
  7. washThe combined organic phase was washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo to a brown gum
  10. customThe gum was purified by FCC

Quellen und Nachweise

ORD-Eintrag
ord-39dbd4967a5c4ab5bd689391859ae0ec
Quelldatensatz
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08907094B2

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