2-Bromoethanol → 2-[4-(4-{5-Chloro-4-[2-(propane-2-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-5-isopropoxy-2-methyl-phenyl)-piperidin-1-yl]-ethanol

HRID 386782ノート

反応式

HRID 386782 の反応式
[Cl:1][C:2]1[C:3]([NH:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[S:33]([CH:36]([CH3:38])[CH3:37])(=[O:35])=[O:34])=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:11][C:10]=2[O:22][CH:23]([CH3:25])[CH3:24])=[N:6][CH:7]=1.Br[CH2:40][CH2:41][OH:42]>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([NH:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[S:33]([CH:36]([CH3:38])[CH3:37])(=[O:35])=[O:34])=[N:4][C:5]([NH:8][C:9]2[C:10]([O:22][CH:23]([CH3:25])[CH3:24])=[CH:11][C:12]([CH:16]3[CH2:21][CH2:20][N:19]([CH2:40][CH2:41][OH:42])[CH2:18][CH2:17]3)=[C:13]([CH3:15])[CH:14]=2)=[N:6][CH:7]=1

参加物

5

反応物 2

HCID 108982-BromoethanolHCID 57379345Ceritinib

生成物 1

HCID 597644602-[4-(4-{5-Chloro-4-[2-(propane-2-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-5-isopropoxy-2-methyl-phenyl)-piperidin-1-yl]-ethanol

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
70 °C

実験手順

5-Chloro-N2-(2-isopropoxy-5-methyl-4-piperidin-4-yl-phenyl)-N4-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine (Example 7, 0.087 mmol) is dissolved in anhydrous DMF (1 mL). TEA (0.04 mL, 0.262 mmol, 3 equiv.) is added followed by 2-bromo-ethanol (0.019 mL, 0.262 mmol, 3 equiv.) dissolved in anhydrous DMF (0.7 mL). The reaction vessel is sealed and heated at 70° C. for 12 h. After cooling to room temperature, the reaction is diluted with ethyl acetate and washed with 1 N aqueous NaOH (5×), the organic layer is then dried over Na2SO4 and filtered. After concentration, the crude product is purified using preparative RP LC-MS to give 2-[4-(4-{5-Chloro-4-[2-(propane-2-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-5-isopropoxy-2-methyl-phenyl)-piperidin-1-yl]-ethanol (72) as a yellow powder: ESMS m/z 602.2 (M+H+).

後処理

  1. customThe reaction vessel is sealed
  2. temperatureAfter cooling to room temperature
  3. washwashed with 1 N aqueous NaOH (5×)
  4. dry with materialthe organic layer is then dried over Na2SO4
  5. filtrationfiltered
  6. concentrationAfter concentration
  7. customthe crude product is purified

出典と根拠

ORDレコード
ord-602c1aac2cfc4e5a858a40fca56c87a7
出典データセット
uspto-grants-2013_02
特許番号
US08372858B2

反応ノート

読み込み中…