Water → 6-tert-Butyl-8-fluoro-2-(2-hydroxymethyl-3-{2-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-pyridin-4-yl}-phenyl)-2H-phthalazin-1-one

HRID 402938Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 402938
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]3[CH:33]=[CH:32][N:31]=[C:30]([NH:34][C:35]4[CH:40]=[CH:39][C:38]([C:41]([N:43]5[CH2:48][CH2:47][O:46][CH2:45][CH2:44]5)=[O:42])=[CH:37][N:36]=4)[CH:29]=3)[C:18]=1[CH2:19][O:20]C(=O)C)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].O>CO>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]3[CH:33]=[CH:32][N:31]=[C:30]([NH:34][C:35]4[CH:40]=[CH:39][C:38]([C:41]([N:43]5[CH2:48][CH2:47][O:46][CH2:45][CH2:44]5)=[O:42])=[CH:37][N:36]=4)[CH:29]=3)[C:18]=1[CH2:19][OH:20])[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Komponenten

5

Edukt 3

HCID 962WaterHCID 11430Potassium CarbonateHCID 86686836acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{2-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-pyridin-4-yl}-benzyl ester

Produkt 1

HCID 866868386-tert-Butyl-8-fluoro-2-(2-hydroxymethyl-3-{2-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-pyridin-4-yl}-phenyl)-2H-phthalazin-1-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

Acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{2-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-pyridin-4-yl}-benzyl ester (200 mg, 0.31 mmol) was dissolved in methanol (10 ml). K2CO3 (86 mg, 0.62 mmol) was added at room temperature, and the mixture was stirred at that temperature for 2 hours. The mixture was poured into water (10 ml), extracted with DCM (100 ml) and then washed with saturated aqueous solution of sodium chloride (100 ml). The combined organic extract was dried over sodium sulfate and concentrated. The residue was purified by silica gel column (petroleum ether:ethyl acetate=1:2). The desired product was obtained as a white solid (130 mg, yield 69%). 1H NMR (300 MHz, MeOD): δ 8.36 (d, J=2.6 Hz, 1H), 8.22-8.18 (m, 2H), 7.73 (d, J=1.5 Hz, 2H), 7.65-7.60 (m, 2H), 7.57-7.51 (m, 1H), 7.50-7.46 (m, 1H), 7.38 (d, J=7.6 Hz, 2H), 7.00 (dd, J=5.2, 1.5 Hz, 1H), 4.36 (s, 2H), 3.59 (s, 8H), 1.36 (d, J=5.7 Hz, 9H). LC-MS: 609[M+1]+, tR=1.407 min. HPLC: 97.79% at 214 nm, 99.31% at 254 nm, tR=3.479 min.

Aufarbeitung

  1. extractionextracted with DCM (100 ml)
  2. washwashed with saturated aqueous solution of sodium chloride (100 ml)
  3. extractionThe combined organic extract
  4. dry with materialwas dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column (petroleum ether:ethyl acetate=1:2)

Quellen und Nachweise

ORD-Eintrag
ord-11fef94ae8c84effb7b7c17e2b80bf54
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08742098B2

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