Morpholine → 2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-N-(1-(cyclopentyl-methylsulfonyl)azetidin-3-yl)-5-fluoropyrimidin-4-amine

HRID 526893ノート

反応式

HRID 526893 の反応式
Cl.[NH:2]1[CH2:5][CH:4]([NH:6][C:7]2[C:12]([F:13])=[CH:11][N:10]=[C:9]([C:14]3[C:22]4[C:17](=[N:18][CH:19]=[C:20]([Cl:23])[CH:21]=4)[N:16](S(C4C=CC(C)=CC=4)(=O)=O)[CH:15]=3)[N:8]=2)[CH2:3]1.CCN(C(C)C)C(C)C.[CH:43]1([CH2:48][S:49](Cl)(=[O:51])=[O:50])[CH2:47][CH2:46][CH2:45][CH2:44]1.N1CCOCC1>ClCCl>[Cl:23][C:20]1[CH:21]=[C:22]2[C:14]([C:9]3[N:8]=[C:7]([NH:6][CH:4]4[CH2:5][N:2]([S:49]([CH2:48][CH:43]5[CH2:47][CH2:46][CH2:45][CH2:44]5)(=[O:51])=[O:50])[CH2:3]4)[C:12]([F:13])=[CH:11][N:10]=3)=[CH:15][NH:16][C:17]2=[N:18][CH:19]=1

参加物

6

反応物 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 2735404Cyclopentylmethanesulfonyl ChlorideHCID 67284924N-(azetidin-3-yl)-2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-amine hydrochloride2 回

生成物 1

HCID 680079372-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-N-(1-(cyclopentyl-methylsulfonyl)azetidin-3-yl)-5-fluoropyrimidin-4-amine収率 88%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a stirred solution of N-(azetidin-3-yl)-2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-amine hydrochloride, 6c, (0.03 g, 0.06 mmol) in dichloromethane (1 mL) was added iPr2NEt (0.33 μL, 1.90 mmol) followed by cyclopentylmethanesulfonyl chloride (0.01 g, 0.06 mmol). The resulting mixture was stirred 30 minutes at room temperature at which time LCMS showed complete reaction. Morpholine (0.20 mL) was added and the solution evaporated to dryness. The resulting residue was dissolved in methanol (2 mL) then treated with 25% sodium methoxide/methanol (0.5 mL) and heated at 60° C. in sealed tube for 10 minutes. The solution was quenched with aqueous saturated NH4Cl solution (0.5 mL) then evaporated to dryness. The resulting residue was dissolved in DMSO and purified by reverse phase HPLC (ammonium formate buffer) to afford 27.4 mg (88% yield) of the desired product, 469, as a solid. LCMS RT=3.1 min, ES+465.

後処理

  1. customreaction
  2. customthe solution evaporated to dryness
  3. dissolutionThe resulting residue was dissolved in methanol (2 mL)
  4. additionthen treated with 25% sodium methoxide/methanol (0.5 mL)
  5. temperatureheated at 60° C. in sealed tube for 10 minutes
  6. customThe solution was quenched with aqueous saturated NH4Cl solution (0.5 mL)
  7. customthen evaporated to dryness
  8. dissolutionThe resulting residue was dissolved in DMSO
  9. custompurified by reverse phase HPLC (ammonium formate buffer)

出典と根拠

ORDレコード
ord-197c53574dd1404fa4837cdecc0c7a7a
出典データセット
uspto-grants-2016_05
特許番号
US09345708B2

反応ノート

読み込み中…