Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 178432530, Verbindung

HRID 1621434

Reaktionsgleichung

Reaktionsgleichung von HRID 1621434
[Cl:1][C:2]1[CH:3]=[C:4]([C:24]2[N:32]=[C:31]([CH3:33])[N:30]=[C:29]3[C:25]=2[N:26]=[CH:27][N:28]3C2CCCCO2)[C:5]([NH:8][C:9]2[C:10]3[CH:11]=[N:12][N:13](C4CCCCO4)[C:14]=3[CH:15]=[CH:16][CH:17]=2)=[N:6][CH:7]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:24]2[N:32]=[C:31]([CH3:33])[N:30]=[C:29]3[C:25]=2[N:26]=[CH:27][NH:28]3)[C:5]([NH:8][C:9]2[C:10]3[CH:11]=[N:12][NH:13][C:14]=3[CH:15]=[CH:16][CH:17]=2)=[N:6][CH:7]=1

Komponenten

4

Edukt 2

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-2×HCID 59548169N-(5-chloro-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine

Produkt 1

HCID 178432530HCID 178432530, VerbindungAusbeute 82 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21226129Dichloromethane methanolLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

A solution of N-(5-chloro-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine (96.8 mg, 178 μmol) in DCM/MeOH (4.0 mL, 1:1) was treated with (+/−)-10-camphorsulfonic acid (91 mg, 391 μmol) and the stirred mixture placed in an oil bath at 40° C. The heater was turned off and the mixture stirred for 16 h. LCMS showed predominantly monodeprotection, so an additional 90 mg of CSA was added (4.4 equiv. total). The mixture was heated at 40° C. until LCMS indicated complete deprotection. The mixture was cooled and purified by ion exchange chromatography (washing with MeOH, eluting off with 2N NH3/MeOH). The product was concentrated, taken up in MeOH (3 mL), sonicated and allowed to stand. N-(5-Chloro-3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indazol-4-amine (55 mg, 82% yield) crystallized out and was collected by filtration as an orange solid. 1H NMR of free base thus obtained gives broad signals, so a small amount was converted to the HCl salt for better 1H NMR analysis by dissolving in MeOH containing 2 drops 2 M aqueous HCl followed by concentration to dryness. HCl salt: 1H NMR (400 MHz, d6-DMSO) δ 11.29 (br. s., 1H); 10.17 (br. s., 1H); 10.04 (s, 1H); 9.27 (d, J=2.69 Hz, 1H); 8.93 (s, 1H); 8.40 (s, 1H); 8.30 (d, J=2.69 Hz, 1H); 7.89 (d, J=9.54 Hz, 1H); 7.52 (d, J=9.54 Hz, 1H); 2.15 (s, 3H). m/z (ESI, +ve) 377.0 (M+H)+.

Aufarbeitung

  1. customthe stirred mixture placed in an oil bath at 40° C
  2. temperatureThe mixture was cooled
  3. custompurified by ion exchange chromatography (washing with MeOH, eluting off with 2N NH3/MeOH)
  4. concentrationThe product was concentrated
  5. customsonicated

Quellen und Nachweise

ORD-Eintrag
ord-c74b02d881e64039b9c0b2b8b5942bc6
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772480B2

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