Methanesulfonyl chloride → Methanesulfonic acid 2-{3-[3-tert-butyl-5-(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}-ureido)-pyrazol-1-yl]-phenoxy}-ethyl ester

HRID 2282605Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2282605
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[C:6]([C:10]1[CH:11]=[C:12]([NH:25][C:26]([NH:28][C@@H:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C@H:32]([O:39][C:40]3[CH:41]=[CH:42][C:43]4[N:44]([C:46]([N:49]5[C@H:54]([CH3:55])[CH2:53][CH2:52][CH2:51][C@@H:50]5[CH3:56])=[N:47][N:48]=4)[CH:45]=3)[CH2:31][CH2:30]2)=[O:27])[N:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][CH2:23][OH:24])[CH:16]=2)[N:14]=1)([CH3:9])([CH3:8])[CH3:7].CCN(C(C)C)C(C)C>C(Cl)Cl>[C:6]([C:10]1[CH:11]=[C:12]([NH:25][C:26]([NH:28][C@@H:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C@H:32]([O:39][C:40]3[CH:41]=[CH:42][C:43]4[N:44]([C:46]([N:49]5[C@H:54]([CH3:55])[CH2:53][CH2:52][CH2:51][C@@H:50]5[CH3:56])=[N:47][N:48]=4)[CH:45]=3)[CH2:31][CH2:30]2)=[O:27])[N:13]([C:15]2[CH:16]=[C:17]([CH:18]=[CH:19][CH:20]=2)[O:21][CH2:22][CH2:23][O:24][S:2]([CH3:1])(=[O:4])=[O:3])[N:14]=1)([CH3:9])([CH3:7])[CH3:8]

Komponenten

5

Edukt 3

HCID 31297Methanesulfonyl chloride3×HCID 81531Diisopropylethylamine3×HCID 896241661-{5-tert-Butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{(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-yl}-urea

Produkt 1

HCID 86687259Methanesulfonic acid 2-{3-[3-tert-butyl-5-(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}-ureido)-pyrazol-1-yl]-phenoxy}-ethyl esterAusbeute 99,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Methane sulfonylchloride (11.0 μL, 0.13 mmol) was added to an ice cold solution of Intermediate 96e (89.0 mg, 0.13 mmol) and DIPEA (27.0 μL, 0.15 mmol) in DCM (1.5 mL). After 1 hour additional DIPEA (27.0 μL, 0.15 mmol) and methane sulfonylchloride (11.0 μL, 0.13 mmol) was added. After a further 1 hour additional DIPEA (27.0 μL, 0.15 mmol) and methane sulfonylchloride (11.0 μL, 0.13 mmol) was added. After 1 hour the reaction was partitioned between DCM and water. The aqueous layer was then extracted with DCM (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo to give the title compound (100 mg, 99%). LCMS (Method 1): Rt 3.73 min, m/z 771 [MH+].

Aufarbeitung

  1. customAfter 1 hour the reaction was partitioned between DCM and water
  2. extractionThe aqueous layer was then extracted with DCM (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-bd901ee4312b42f781ed797a1cce8442
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09139584B2

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