Water → 4-[2-[2-(Difluoromethyl)-4-methoxybenzimidazol-1-yl]-9-(1-methylsulfonylpiperidin-4-yl)purin-6-yl]morpholine

HRID 516417Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 516417
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[F:6][CH:7]([F:40])[C:8]1[N:12]([C:13]2[N:21]=[C:20]3[C:16]([N:17]=[CH:18][N:19]3[CH:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[C:15]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[N:14]=2)[C:11]2[CH:34]=[CH:35][CH:36]=[C:37]([O:38][CH3:39])[C:10]=2[N:9]=1.C([O-])([O-])=O.[K+].[K+].O>C(Cl)Cl>[F:40][CH:7]([F:6])[C:8]1[N:12]([C:13]2[N:21]=[C:20]3[C:16]([N:17]=[CH:18][N:19]3[CH:22]3[CH2:27][CH2:26][N:25]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:24][CH2:23]3)=[C:15]([N:28]3[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)[N:14]=2)[C:11]2[CH:34]=[CH:35][CH:36]=[C:37]([O:38][CH3:39])[C:10]=2[N:9]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 666981762-[2-(Difluoromethyl)-4-methoxy-1h-benzimidazol-1-yl]-6-(4-morpholinyl)-9-(4-piperidinyl)-9h-purine

Produkt 1

HCID 469176534-[2-[2-(Difluoromethyl)-4-methoxybenzimidazol-1-yl]-9-(1-methylsulfonylpiperidin-4-yl)purin-6-yl]morpholineAusbeute 88,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Methanesulfonyl chloride (0.08 mL, 1.03 mmol) was added dropwise to a mixture of the above amine (102 mg, 0.211 mmol) and powdered K2CO3 (263 mg, 1.90 mmol) in CH2Cl2 (10 mL) at 0° C. The mixture was allowed to warm to room temperature and was stirred for 5 hrs. Water was added, the phases were separated, and the aqueous phase was extracted with CH2Cl2. The combined organic extracts were dried (Na2SO4) and the solvent was removed under vacuum. Recrystallization from CH2Cl2/MeOH gave 2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-9-[1-(methylsulfonyl)-4-piperidinyl]-6-(4-morpholinyl)-9H-purine (105 mg, 88%): mp 236-239° C.; 1H NMR (CDCl3) δ 7.84 (s, 1H), 7.76 (dd, J=8.4, 0.5 Hz, 1H), 7.42 (t, JHF=53.6 Hz, 1H), 7.36 (t, J=8.2 Hz, 1H), 6.81 (d, J=7.8 Hz, 1H), 4.57 (tt, J=11.7, 4.4 Hz, 1H), 4.38 (br s, 4H), 4.09 (m, 2H), 4.06 (s, 3H), 3.88 (t, J=4.8 Hz, 4H), 2.96 (dt, J=12.5, 2.8 Hz, 2H), 2.88 (s, 3H), 2.35-2.20 (m, 4H); Anal. Calcd. for C24H28F2N8O4S: C, 51.2; H, 5.0; N, 19.9. Found: C, 51.0; H, 4.9; N, 19.7%.

Aufarbeitung

  1. customthe phases were separated
  2. extractionthe aqueous phase was extracted with CH2Cl2
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. customthe solvent was removed under vacuum
  5. customRecrystallization from CH2Cl2/MeOH

Quellen und Nachweise

ORD-Eintrag
ord-d69f79d63d84437599b3f5516a6406c0
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108980B2

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