Acetone → 3-[6-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-4,5-dihydro-3H pyrimido[5',4':4,5]thieno[2,3-e]indazol-3-yl]propane-1,2-diol

HRID 222044

Reaktionsgleichung

Reaktionsgleichung von HRID 222044
C([N:4]1[C:12]2C[CH2:10][C:9]3[C:13]4[C:14](=[N:16][CH:17]=[N:18][C:19]=4[NH:20][C:21]4[CH:26]=[CH:25][C:24]([O:27][CH2:28][C:29]5[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[CH:30]=5)=[C:23]([Cl:36])[CH:22]=4)[S:15][C:8]=3[C:7]=2C=N1)C=C.O.C[N+:39]1([O-])[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.S([O-])([O-])=O.[Na+].[Na+].C[C:53](C)=[O:54]>O.[Os](=O)(=O)(=O)=O>[Cl:36][C:23]1[CH:22]=[C:21]([NH:20][C:19]2[C:13]3[C:9]4[CH2:10][CH2:43][C:44]5[N:39]([CH2:40][CH:41]([OH:42])[CH2:53][OH:54])[N:4]=[CH:12][C:7]=5[C:8]=4[S:15][C:14]=3[N:16]=[CH:17][N:18]=2)[CH:26]=[CH:25][C:24]=1[O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[CH:30]=1

Komponenten

7

Edukt 4

HCID 180AcetoneHCID 24437Sodium SulfiteHCID 2724197N-Methylmorpholine N-oxide monohydrateHCID 58346706HCID 58346706, Verbindung

Produkt 1

HCID 583465743-[6-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-4,5-dihydro-3H pyrimido[5',4':4,5]thieno[2,3-e]indazol-3-yl]propane-1,2-diolAusbeute 8,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 30318Osmium TetroxideKatalysatorHCID 962WaterLösungsmittel

Versuchsvorschrift

To a solution of 3-allyl-N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-4,5-dihydro-3H-pyrimido[5′,4′:4,5]thieno[2,3-e]indazol-6-amine (300 mg, 0.52 mmol) and 4-methylmorpholine N-oxide monohydrate (133 mg, 1.14 mmol, 2.2 eq) in acetone (5 mL) and water (0.5 mL) was added a catalytic amount of osmium (VIII) tetraoxide (10 mg, 2.5 w % in t-BuOH). The reaction mixture was stirred at rt for 16 h. Sodium sulfite (1 g) was added to the stirred solution and the mixture was stirred for an additional 1 h. The mixture was passed through a pad of silicon gel and Celite mixture. The pad was washed with EtOAc (2×10 mL). The combined EtOAc layers were dried over sodium sulfate and then concentrated in vacuo. The residue was then purified by preparative-HPLC to give 3-[6-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-4,5-dihydro-3H pyrimido[5′,4′:4,5]thieno[2,3-e]indazol-3-yl]propane-1,2-diol (25.5 mg, 8.9%) as a white solid. 1H NMR (CD3CN) δ 8.31 (s, 1H), 7.82 (d, J=2.6 Hz, 1H), 7.59 (s, 1H), 7.45 (dd, J=2.3, 8.9 Hz, 1H), 7.45 (m, 1H), 7.33 (t, 1H), 7.28 (d, J=10 Hz, 1H), 7.14 (d, J=9 Hz, 1H), 7.12 (m, 1H), 5.23 (s, 2H), 4.25 (m, 1H), 3.67 (m, 4H), 3.43 (t, 2H), 3.15 (t, 2H); LCMS RT=3.17 min, [M+H]+=552.0

Aufarbeitung

  1. stirringthe mixture was stirred for an additional 1 h
  2. washThe pad was washed with EtOAc (2×10 mL)
  3. dry with materialThe combined EtOAc layers were dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was then purified by preparative-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-129e44a4c28544c4b436f1b993b061d7
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08207172B2

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