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Methanesulfonyl chloride → 2-{3-[3-(1-{[tert-Butyl(diphenyl)silyl]oxy}-2-methylpropan-2-yl)-5-({[(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]carbamoyl}amino)-1H-pyrazol-1-yl]phenoxy}ethyl methanesulfonate

HRID 1402441
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1402441
[Si:1]([O:18][CH2:19][C:20]([C:23]1[CH:27]=[C:26]([NH:28][C:29]([NH:31][C@@H:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[C@H:35]([O:42][C:43]3[CH:44]=[CH:45][C:46]4[N:47]([C:49]([N:52]5[CH2:57][CH2:56][CH2:55][CH2:54][C@@H:53]5[CH3:58])=[N:50][N:51]=4)[CH:48]=3)[CH2:34][CH2:33]2)=[O:30])[N:25]([C:59]2[CH:64]=[CH:63][CH:62]=[C:61]([O:65][CH2:66][CH2:67][OH:68])[CH:60]=2)[N:24]=1)([CH3:22])[CH3:21])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[CH3:78][S:79](Cl)(=[O:81])=[O:80]>C(Cl)Cl.C(=O)(O)[O-].[Na+]>[CH3:78][S:79]([O:68][CH2:67][CH2:66][O:65][C:61]1[CH:62]=[CH:63][CH:64]=[C:59]([N:25]2[C:26]([NH:28][C:29](=[O:30])[NH:31][C@@H:32]3[C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[C@H:35]([O:42][C:43]4[CH:44]=[CH:45][C:46]5[N:47]([C:49]([N:52]6[CH2:57][CH2:56][CH2:55][CH2:54][C@@H:53]6[CH3:58])=[N:50][N:51]=5)[CH:48]=4)[CH2:34][CH2:33]3)=[CH:27][C:23]([C:20]([CH3:21])([CH3:22])[CH2:19][O:18][Si:1]([C:14]([CH3:16])([CH3:15])[CH3:17])([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[N:24]2)[CH:60]=1)(=[O:81])=[O:80]
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Komponenten

6

Edukt 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 866872901-{3-(1-{[tert-Butyl(diphenyl)silyl]oxy}-2-methylpropan-2-yl)-1-[3-(2-hydroxyethoxy)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

Produkt 1

HCID 86687289
2-{3-[3-(1-{[tert-Butyl(diphenyl)silyl]oxy}-2-methylpropan-2-yl)-5-({[(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]carbamoyl}amino)-1H-pyrazol-1-yl]phenoxy}ethyl methanesulfonate
Ausbeute 58 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittel2×HCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

A solution of Intermediate 153h (214 mg, 0.23 mmol) in DCM (2.3 mL) was treated with DIPEA (0.12 mL, 0.69 mmol) then methanesulfonyl chloride (0.037 mL, 0.48 mmol). After 30 mins the mixture was diluted with DCM and saturated aqueous sodium bicarbonate solution. The phases were separated and the aqueous layer was extracted with DCM (×2). The combined organic phase was washed with water, saturated aqueous sodium bicarbonate solution and brine, dried (Na2SO4) and concentrated in vacuo to an orange gum. The gum was purified by FCC, using 0-8% MeOH in DCM, to give the title compound as a pale brown glass (134 mg, 58%). LCMS (Method 3): Rt 5.18 min, m/z 1011.7 [MH+].

Aufarbeitung

  1. customThe phases were separated
  2. extractionthe aqueous layer was extracted with DCM (×2)
  3. washThe combined organic phase was washed with water, saturated aqueous sodium bicarbonate solution and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo to an orange gum
  6. customThe gum was purified by FCC

Quellen und Nachweise

ORD-Eintrag
ord-5258f8de8a794be284fb6753ad7a5327
Quelldatensatz
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08907094B2

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