Dimethylformamide → 2-((R)-1-(4-hydroxycyclohexyl)ethylamino)-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile

HRID 40839ノート

反応式

HRID 40839 の反応式
[NH2:1][C@@H:2]([CH:4]1[CH2:9][CH2:8][CH:7]([OH:10])[CH2:6][CH2:5]1)[CH3:3].CN(C=O)C.C(N(C(C)C)CC)(C)C.Cl[C:26]1[N:31]=[C:30]([C:32]2[C:40]3[C:35](=[N:36][CH:37]=[C:38]([C:41]([F:44])([F:43])[F:42])[CH:39]=3)[N:34]([S:45]([C:48]3[CH:54]=[CH:53][C:51]([CH3:52])=[CH:50][CH:49]=3)(=[O:47])=[O:46])[CH:33]=2)[C:29]([C:55]#[N:56])=[CH:28][N:27]=1>C1COCC1>[OH:10][CH:7]1[CH2:8][CH2:9][CH:4]([C@H:2]([NH:1][C:26]2[N:31]=[C:30]([C:32]3[C:40]4[C:35](=[N:36][CH:37]=[C:38]([C:41]([F:43])([F:44])[F:42])[CH:39]=4)[N:34]([S:45]([C:48]4[CH:54]=[CH:53][C:51]([CH3:52])=[CH:50][CH:49]=4)(=[O:46])=[O:47])[CH:33]=3)[C:29]([C:55]#[N:56])=[CH:28][N:27]=2)[CH3:3])[CH2:5][CH2:6]1

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 55285649(R)-4-(1-Aminoethyl)cyclohexan-1-olHCID 594144402-chloro-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile

生成物 1

HCID 594144152-((R)-1-(4-hydroxycyclohexyl)ethylamino)-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile収率 88.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

4-((R)-1-aminoethyl)cyclohexanol (309.4 mg, 2.16 mmol) was dissolved in THF (10 mL) and DMF (4 mL) and stirred over molecular sieves for 10 minutes. Diisopropylethylamine (376.3 μL, 2.160 mmol) was added, followed by 2-chloro-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile (516.1 mg, 1.080 mmol). The reaction mixture was stirred under nitrogen at ambient temperature for 18 hours. The molecular sieves was removed by filtration and washed with EtOAc. The filtrate was washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography (ISCO Companion□, 80 g column, 0-100% EtOAc/DCM) to afford the title compound as a yellow solid (558 mg, 88% yield).

後処理

  1. customThe molecular sieves was removed by filtration
  2. washwashed with EtOAc
  3. washThe filtrate was washed with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified on silica gel by flash column chromatography (ISCO Companion□, 80 g column, 0-100% EtOAc/DCM)

出典と根拠

ORDレコード
ord-e8ee08db6ba7414a9022f34ac7f5cd07
出典データセット
uspto-grants-2013_09
特許番号
US08530489B2

反応ノート

読み込み中…