2-Chloro-5-methoxypyrimidine → rac-cis-(2-(((5-Methoxypyrimidin-2-yl)amino)methyl)-3-methylpiperidin-1-yl) (5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone

HRID 60847

反応式

HRID 60847 の反応式
[NH2:1][CH2:2][C@H:3]1[C@@H:8]([CH3:9])[CH2:7][CH2:6][CH2:5][N:4]1[C:10]([C:12]1[N:13]=[C:14]([CH3:24])[S:15][C:16]=1[C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)=[O:11].Cl[C:26]1[N:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][N:27]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:33][O:32][C:29]1[CH:28]=[N:27][C:26]([NH:1][CH2:2][C@H:3]2[C@@H:8]([CH3:9])[CH2:7][CH2:6][CH2:5][N:4]2[C:10]([C:12]2[N:13]=[C:14]([CH3:24])[S:15][C:16]=2[C:17]2[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=2)=[O:11])=[N:31][CH:30]=1

参加物

7

反応物 4

HCID 5890582-Chloro-5-methoxypyrimidineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 117727897Rac-cis-(2-(aminomethyl)-3-methylpiperidin-1-yl)(5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone

生成物 1

HCID 131737137rac-cis-(2-(((5-Methoxypyrimidin-2-yl)amino)methyl)-3-methylpiperidin-1-yl) (5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
70 °C

実験手順

A mixture of rac-cis-(2-(aminomethyl)-3-methylpiperidin-1-yl)(5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone, 2-chloro-5-methoxypyrimidine, Pd2dba3, BINAP, and NaOtBu in toluene was purged with argon, and then stirred at 70° C. for 72 h. The reaction was cooled, filtered through a pad of silica gel and concentrated in vacuo. The crude reaction mixture was purified by reverse-phase preparative HPLC to afford the title compound. MS (ESI) 456.2 (M+H).

後処理

  1. customwas purged with argon
  2. temperatureThe reaction was cooled
  3. filtrationfiltered through a pad of silica gel
  4. concentrationconcentrated in vacuo
  5. customThe crude reaction mixture
  6. customwas purified by reverse-phase preparative HPLC

出典と根拠

ORDレコード
ord-38867a59a69a484dab80174d17ba2d0e
出典データセット
uspto-grants-2016_09
特許番号
US09440982B2

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