1,2-Dichloroethane → 6-tert-butyl-2-(3-{5-[5-(1,1-dimethyl-2-morpholin-4-yl-2-oxo-ethyl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl}-2-hydroxymethyl-phenyl)-8-fluoro-2H-phthalazin-1-one

HRID 2069724Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2069724
[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[C:18]([CH2:44][OH:45])=[C:19]([C:23]3[CH:24]=[C:25]([NH:31][C:32]4[N:37]=[CH:36][C:35]([C:38]([CH3:43])([CH3:42])[C:39](O)=[O:40])=[CH:34][CH:33]=4)[C:26](=[O:30])[N:27]([CH3:29])[CH:28]=3)[CH:20]=[CH:21][CH:22]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[NH:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1.C(Cl)CCl.[Cl-].[NH4+]>CN(C1C=CN=CC=1)C.C(Cl)Cl.C(OCC)(=O)C>[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:22]=[CH:21][CH:20]=[C:19]([C:23]3[CH:24]=[C:25]([NH:31][C:32]4[CH:33]=[CH:34][C:35]([C:38]([CH3:43])([CH3:42])[C:39]([N:46]5[CH2:51][CH2:50][O:49][CH2:48][CH2:47]5)=[O:40])=[CH:36][N:37]=4)[C:26](=[O:30])[N:27]([CH3:29])[CH:28]=3)[C:18]=1[CH2:44][OH:45])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2]

Komponenten

8

Edukt 4

HCID 111,2-DichloroethaneHCID 8083MorpholineHCID 25517Ammonium ChlorideHCID 469088042-(6-{5-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-2-oxo-1,2-dihydro-pyridin-3-ylamino}-pyridin-3-yl)-2-methyl-propionic acid

Produkt 1

HCID 469088056-tert-butyl-2-(3-{5-[5-(1,1-dimethyl-2-morpholin-4-yl-2-oxo-ethyl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl}-2-hydroxymethyl-phenyl)-8-fluoro-2H-phthalazin-1-oneAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

2-(6-{5-[3-(6-tert-Butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-2-oxo-1,2-dihydro-pyridin-3-ylamino}-pyridin-3-yl)-2-methyl-propionic acid (50 mg, 0.08 mmol), morpholine (11 mg, 0.12 mmol), EDC (23 mg, 0.12 mmol), and DMAP (15 mg, 0.12 mmol) were dissolved in 1 ml of DCM and stirred at room temperature under nitrogen overnight. Ethyl acetate and saturated aqueous ammonium chloride were added and the layers were separated. The organic layer was washed with dilute ammonium chloride, then saturated aqueous sodium bicarbonate, dried, and concentrated. The crude product was purified by flash chromatography using a gradient of 0% to 10% methanol in DCM to give 40 mg (74%) of 6-tert-butyl-2-(3-{5-[5-(1,1-dimethyl-2-morpholin-4-yl-2-oxo-ethyl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl}-2-hydroxymethyl-phenyl)-8-fluoro-2H-phthalazin-1-one. MS: (M+H)+=681. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.43 (s, 9 H) 1.53 (s, 6 H) 3.45 (br. s, 7 H) 3.71 (s, 3 H) 3.76 (br. s., 1H) 4.41 (br. s., 2 H) 6.85 (d, J=8.69 Hz, 1 H) 7.31-7.43 (m, 3 H) 7.48-7.61 (m, 4 H) 7.96 (s, 1 H) 8.15 (s, 1 H) 8.30 (s, 1 H) 8.69 (s, 1 H).

Aufarbeitung

  1. customthe layers were separated
  2. washThe organic layer was washed with dilute ammonium chloride
  3. dry with materialsaturated aqueous sodium bicarbonate, dried
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-6a2a270749644b0cab8bdfcd0cda3273
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08299077B2

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