Imatinib amine → HCID 67533795、化合物

HRID 273297ノート

反応式

HRID 273297 の反応式
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[NH:9][C:10]1[N:15]=[C:14]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[CH:13]=[CH:12][N:11]=1.C[O:23][C:24](=O)[C:25]1[CH:30]=[CH:29][C:28]([CH:31]([Cl:33])[Cl:32])=[CH:27][CH:26]=1.C[Al](C)C>C1(C)C=CC=CC=1>[Cl:32][CH:31]([Cl:33])[C:28]1[CH:27]=[CH:26][C:25]([C:24]([NH:8][C:5]2[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([NH:9][C:10]3[N:15]=[C:14]([C:16]4[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=4)[CH:13]=[CH:12][N:11]=3)[CH:4]=2)=[O:23])=[CH:30][CH:29]=1

参加物

5

反応物 3

HCID 9965429Imatinib amineHCID 10798892Benzoic acid, 4-(dichloromethyl)-, methyl esterHCID 16682925Trimethylaluminum

生成物 1

HCID 67533795HCID 67533795、化合物

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
45 °C

実験手順

To a suspension of 4-methyl-N*3*-(4-pyridin-3-yl-pyrimidin-2-yl)-benzene-1,3-diamine (2.00 g mg, 7.21 mmol) in toluene (22 ml) at 45° C. under an atmosphere of argon is added sequentially 4-dichloromethyl-benzoic acid methyl ester (1.90 g, 8.67 mmol) and AlMe3 (2 M in toluene, 12.6 ml, 25.2 mmol). The resulting brown solution is stirred at 45° C. for a period of 3.5 hrs. The reaction mixture is then cooled to 0° C. and quenched by slow addition of a saturated aqueous solution of Rochelle salt (70 ml) which causes the precipitation of the crude product. t-Butyl methyl ether (150 ml) and methylene chloride (100 ml) are added sequentially to the suspension which are then washed with aqueous saturated NaHCO3 (100 ml) and aqueous saturated NaCl (100 ml). The aqueous phases are back-extracted with t-butyl methyl ether (100 ml). The crude product, which is contained in the combined organic phases, is filtered off with suction, washed with t-butyl methyl ether and dried in vacuo. Yield: 3.35 g of the title compound, 84% of theory, as beige crystals, (HPLC: 91% area).

後処理

  1. temperatureThe reaction mixture is then cooled to 0° C.
  2. customquenched by slow addition of a saturated aqueous solution of Rochelle salt (70 ml) which
  3. customthe precipitation of the crude product
  4. additiont-Butyl methyl ether (150 ml) and methylene chloride (100 ml) are added sequentially to the suspension which
  5. washare then washed with aqueous saturated NaHCO3 (100 ml) and aqueous saturated NaCl (100 ml)
  6. extractionThe aqueous phases are back-extracted with t-butyl methyl ether (100 ml)
  7. filtrationis filtered off with suction
  8. washwashed with t-butyl methyl ether
  9. customdried in vacuo

出典と根拠

ORDレコード
ord-fea1ab82bcff4fe4be20be0b5a11e35d
出典データセット
uspto-grants-2008_11
特許番号
US07456283B2

反応ノート

読み込み中…