Methanesulfonic Acid → 6-chloro-2-(6-fluoro-1H-benzo[d]imidazol-1-yl)-9-((R)-8-fluorochroman-4-yl)-7H-purin-8(9H)-one

HRID 600428Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 600428
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[NH:9][C:10]1[N:18]=[C:17]2[C:13]([NH:14][C:15](=[O:30])[N:16]2[C@H:19]2[C:28]3[C:23](=[C:24]([F:29])[CH:25]=[CH:26][CH:27]=3)[O:22][CH2:21][CH2:20]2)=[C:12]([Cl:31])[N:11]=1.[CH3:32]OC(OC)OC.CS(O)(=O)=O>CO>[Cl:31][C:12]1[N:11]=[C:10]([N:9]2[C:3]3[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=3[N:1]=[CH:32]2)[N:18]=[C:17]2[C:13]=1[NH:14][C:15](=[O:30])[N:16]2[C@H:19]1[C:28]2[C:23](=[C:24]([F:29])[CH:25]=[CH:26][CH:27]=2)[O:22][CH2:21][CH2:20]1

Komponenten

5

Edukt 3

HCID 6395Methanesulfonic AcidHCID 9005Trimethyl orthoformateHCID 86622939(R)-2-(2-amino-5-fluorophenylamino)-6-chloro-9-(8-fluorochroman-4-yl)-7H-purin-8(9H)-one

Produkt 1

HCID 576126986-chloro-2-(6-fluoro-1H-benzo[d]imidazol-1-yl)-9-((R)-8-fluorochroman-4-yl)-7H-purin-8(9H)-oneAusbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

To a round bottom flask containing (R)-2-(2-amino-5-fluorophenylamino)-6-chloro-9-(8-fluorochroman-4-yl)-7H-purin-8(9H)-one (0.65 mmol) was added anhydrous methanol (45 mL), followed by anhydrous trimethylorthoformate (5 mL) and methane sulfonic acid (0.1 mL) and the reaction mixture was stirred under Ar at room temperature until it was complete (HPLC monitoring). Preparative HPLC purification, after evaporation of solvent and drying, provided the desired product (184 mg, 62% yield on two steps), as a white solid. 1H NMR (300 MHz, CDCl3) δ, ppm: 9.38 (br s, 1H), 9.01 (s, 1H), 7.84-7.79 (m, 1H), 7.64-7.60 (m, 1H), 7.20-7.13 (m, 1H), 7.10-7.03 (m, 1H), 6.79-6.67 (m, 2H), 5.97-5.92 (m, 1H), 4.68-4.62 (m, 1H), 4.51-4.40 (m, 1H), 2.95-2.83 (m, 1H), 2.41-2.36 (m, 1H); MS (EI) m/z 454.9 (MH)+.

Aufarbeitung

  1. customPreparative HPLC purification
  2. customafter evaporation of solvent
  3. customdrying

Quellen und Nachweise

ORD-Eintrag
ord-a36aa3d616cf499d84d90aa44a5e7ed3
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902187B2

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