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

反応式

HRID 449657 の反応式
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]

参加物

4

反応物 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

生成物 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

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-43ab6ad2cbc24608a61bec11f2e22a05
出典データセット
uspto-grants-2013_07
特許番号
US08481540B2

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