Methanesulfonyl chloride → Methanesulfonic acid 2-{3-[5-(3-{(1S,4R)-4-[3-(4-aza-spiro[2.5]oct-4-yl)-[1,2,4] triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-3-tert-butyl-pyrazol-1-yl]-phenoxy}-ethyl ester

HRID 1402417Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1402417
[CH2:1]1[C:3]2([CH2:8][CH2:7][CH2:6][CH2:5][N:4]2[C:9]2[N:13]3[CH:14]=[C:15]([O:18][C@H:19]4[C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[C@@H:22]([NH:29][C:30]([NH:32][C:33]5[N:34]([C:42]6[CH:47]=[CH:46][CH:45]=[C:44]([O:48][CH2:49][CH2:50][OH:51])[CH:43]=6)[N:35]=[C:36]([C:38]([CH3:41])([CH3:40])[CH3:39])[CH:37]=5)=[O:31])[CH2:21][CH2:20]4)[CH:16]=[CH:17][C:12]3=[N:11][N:10]=2)[CH2:2]1.CCN(C(C)C)C(C)C.[CH3:61][S:62](Cl)(=[O:64])=[O:63].C([O-])(O)=O.[Na+]>C(Cl)Cl.O>[CH2:2]1[C:3]2([CH2:8][CH2:7][CH2:6][CH2:5][N:4]2[C:9]2[N:13]3[CH:14]=[C:15]([O:18][C@H:19]4[C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[C@@H:22]([NH:29][C:30](=[O:31])[NH:32][C:33]5[N:34]([C:42]6[CH:43]=[C:44]([CH:45]=[CH:46][CH:47]=6)[O:48][CH2:49][CH2:50][O:51][S:62]([CH3:61])(=[O:64])=[O:63])[N:35]=[C:36]([C:38]([CH3:41])([CH3:39])[CH3:40])[CH:37]=5)[CH2:21][CH2:20]4)[CH:16]=[CH:17][C:12]3=[N:11][N:10]=2)[CH2:1]1

Komponenten

7

Edukt 4

HCID 31297Methanesulfonyl chloride2×HCID 81531Diisopropylethylamine2×HCID 516892Sodium BicarbonateHCID 866872671-{(1S,4R)-4-[3-(4-Aza-spiro[2.5]oct-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-3-{5-tert-butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-urea

Produkt 1

HCID 86687268Methanesulfonic acid 2-{3-[5-(3-{(1S,4R)-4-[3-(4-aza-spiro[2.5]oct-4-yl)-[1,2,4] triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-3-tert-butyl-pyrazol-1-yl]-phenoxy}-ethyl esterAusbeute 100 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A yellow-orange solution of Intermediate 148f (137 mg, 0.198 mmol), DIPEA (0.10 mL, 0.60 mmol) and methanesulfonyl chloride (45 mg, 0.40 mmol) in DCM (5 mL) was stirred at 0° C. for 30 min, and at RT for 30 min. DIPEA (0.052 mL, 0.30 mmol) and MsCl (23 mg, 0.20 mmol) were added and the solution stirred at RT for 30 min. Water (2 mL) and sat. aq. NaHCO3 solution (2 mL) were added and the mixture shaken. The aqueous was extracted with DCM (5 mL), then the combined organics passed through a hydrophobic fit and concentrated in vacuo to leave the title compound as a yellow solid (100%). LCMS (Method 3): Rt 3.80 min, m/z 769 [MH+].

Aufarbeitung

  1. stirringthe mixture shaken
  2. extractionThe aqueous was extracted with DCM (5 mL)
  3. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-4e5c0631d80d46daa187e36b95be50f4
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08907094B2

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