6-Chloro-4-(5-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-pyridin-2-ylamino)-2-methyl-2H-pyridazin-3-one → 6-tert-Butyl-8-fluoro-2-{2-hydroxymethyl-3-[5-(5-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-phenyl}-2H-phthalazin-1-one

HRID 449657

Reaktionsgleichung

Reaktionsgleichung von HRID 449657
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][N:18]([CH2:20][CH2:21][O:22][CH3:23])[CH3:19])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.ClC1C=C(NC2C=CC(CN3CCN(C)CC3)=CN=2)C(=O)N(C)N=1.C([O:51][CH2:52][C:53]1[C:58]([N:59]2[N:68]=[CH:67][C:66]3[C:61](=[C:62]([F:73])[CH:63]=[C:64]([C:69]([CH3:72])([CH3:71])[CH3:70])[CH:65]=3)[C:60]2=[O:74])=[CH:57][CH:56]=[CH:55][C:54]=1[B-](F)(F)F)(=O)C.[K+]>>[C:69]([C:64]1[CH:65]=[C:66]2[C:61](=[C:62]([F:73])[CH:63]=1)[C:60](=[O:74])[N:59]([C:58]1[CH:57]=[CH:56][CH:55]=[C:54]([C:2]3[CH:3]=[C:4]([NH:10][C:11]4[CH:16]=[CH:15][C:14]([CH2:17][N:18]([CH2:20][CH2:21][O:22][CH3:23])[CH3:19])=[CH:13][N:12]=4)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=3)[C:53]=1[CH2:52][OH:51])[N:68]=[CH:67]2)([CH3:72])([CH3:70])[CH3:71]

Komponenten

4

Edukt 3

HCID 667422656-Chloro-4-(5-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-pyridin-2-ylamino)-2-methyl-2H-pyridazin-3-oneHCID 667423596-Chloro-2-methyl-4-(5-((4-methylpiperazin-1-yl)methyl)pyridin-2-ylamino)pyridazin-3(2H)-oneHCID 87134390potassium (2-(acetoxymethyl)-3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)phenyl)trifluoroborate

Produkt 1

HCID 566560546-tert-Butyl-8-fluoro-2-{2-hydroxymethyl-3-[5-(5-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-phenyl}-2H-phthalazin-1-one

Versuchsvorschrift

6-tert-Butyl-8-fluoro-2-{2-hydroxymethyl-3-[5-(5-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-phenyl}-2H-phthalazin-1-one was prepared using the general procedure described in example 41 substituting 6-Chloro-4-(5-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-pyridin-2-ylamino)-2-methyl-2H-pyridazin-3-one for 6-chloro-2-methyl-4-(5-((4-methylpiperazin-1-yl)methyl)pyridin-2-ylamino)pyridazin-3(2H)-one in step 3. For the Suzuki reaction, potassium (2-(acetoxymethyl)-3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)phenyl)trifluoroborate (Eq: 1.2) was used in place of 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate. After removal of the acetate protecting group using potassium carbonate in methanol, water was added dropwise and the reaction was stirred at room temperature overnight. The solid that formed was filtered, washed with water then ether and dried in a vacuum oven to give 52 mgs of a crystalline white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.38 (s, 9H) 2.13 (s, 3H) 2.47 (s, 2H) 3.22 (s, 3H) 3.39-3.49 (m, 4H) 3.79 (s, 3H) 4.43 (br. s., 2H) 4.58 (br. s., 1H) 7.41-7.65 (m, 5H) 7.75 (d, J=13.22 Hz, 1H) 7.87 (s, 1H) 8.17 (s, 1H) 8.46-8.59 (m, 2H) 9.40 (s, 1H). MS: (M+H)+=628.

Aufarbeitung

  1. customAfter removal of the acetate protecting group
  2. additionwas added dropwise
  3. customThe solid that formed
  4. filtrationwas filtered
  5. washwashed with water
  6. dry with materialether and dried in a vacuum oven

Quellen und Nachweise

ORD-Eintrag
ord-43ab6ad2cbc24608a61bec11f2e22a05
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481540B2

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