N-methylthiophen-3-amine → HCID 68108739、化合物

HRID 1809740ノート

反応式

HRID 1809740 の反応式
[C:1]([O:5][C:6](=[O:39])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[N:20]=[C:19]3[N:21]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[N:22]=[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26](Br)[N:25]=4)[C:18]3=[CH:17][N:16]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[S:40]1[CH:44]=[CH:43][C:42](NC)=[CH:41]1.[CH3:47][N:48](C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.C(O[Na])(C)(C)C>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].O1CCOCC1>[C:1]([O:5][C:6](=[O:39])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[N:20]=[C:19]3[N:21]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[N:22]=[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([NH:48][CH2:47][C:42]5[CH:43]=[CH:44][S:40][CH:41]=5)[N:25]=4)[C:18]3=[CH:17][N:16]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 642344N-methylthiophen-3-amineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 86667966{4-[3-(6-bromo-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino]-cyclohexyl}-carbamic acid tert-butyl esterHCID 178418730sodium 2-methylpropan-2-olate

生成物 1

HCID 68108739HCID 68108739、化合物

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
102 °C

実験手順

A sealed tube was charged with {4-[3-(6-bromo-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (from Example 33 supra) (500 mg, 0.809 mmol), thiophen-3-yl-methylamine (118 mg, 1.044 mmol), Pd2(dba)3 (47 mg, 0.0817 mmol), DavePhos (64 mg, 0.163 mmol), t-BuONa (109 mg, 1.135 mmol) and dioxane (20 mL). The mixture was stirred at 102° C. under an atmosphere of N2 for 12 hours. After cooling to room temperature, the mixture was filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 12 g, 200-300 mesh, eluting with petroleum ether:ethyl acetate, 3:1) to give {4-[3-{6-[(thiophen-3-ylmethyl)-amino]-pyridin-2-yl}-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester. (Yield 415 mg, 79%).

後処理

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography (silica gel, 12 g, 200-300 mesh, eluting with petroleum ether:ethyl acetate, 3:1)

出典と根拠

ORDレコード
ord-b92f9d4f68b14fc083baf5c6e44cd737
出典データセット
uspto-grants-2013_01
特許番号
US08362023B2

反応ノート

読み込み中…