Isopropanol → 5-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-5-fluoropyrimidin-2-ylamino)-2-(4-isopropylpiperazin-1-yl)benzonitrile

HRID 633451ノート

反応式

HRID 633451 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:17][C@H:16]3[N:12]([CH2:13][CH2:14][CH2:15]3)[C:11]([CH3:19])([CH3:18])[CH2:10]2)[C:5]([F:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:23]=[CH:24][C:25]([N:30]2[CH2:35][CH2:34][N:33]([CH:36]([CH3:38])[CH3:37])[CH2:32][CH2:31]2)=[C:26]([CH:29]=1)[C:27]#[N:28].C[CH:40]([OH:42])C>>[NH3:3].[CH3:40][OH:42].[CH3:18][C:11]1([CH3:19])[CH2:10][C@H:9]([NH:8][C:6]2[C:5]([F:20])=[CH:4][N:3]=[C:2]([NH:21][C:22]3[CH:23]=[CH:24][C:25]([N:30]4[CH2:35][CH2:34][N:33]([CH:36]([CH3:38])[CH3:37])[CH2:32][CH2:31]4)=[C:26]([CH:29]=3)[C:27]#[N:28])[N:7]=2)[CH2:17][C@H:16]2[N:12]1[CH2:13][CH2:14][CH2:15]2

参加物

5

反応物 3

HCID 3776IsopropanolHCID 612969195-Amino-2-(4-isopropylpiperazin-1-yl)benzonitrileHCID 86704490(7R,8aS)-N-(2-chloro-5-fluoropyrimidin-4-yl)-5,5-dimethyloctahydroindolizin-7-amine

生成物 2

HCID 21705897Ammonia methanol収率 1%HCID 867045405-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-5-fluoropyrimidin-2-ylamino)-2-(4-isopropylpiperazin-1-yl)benzonitrile収率 71%

実験手順

A mixture of (7R,8aS)-N-(2-chloro-5-fluoropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine (163 mg, 0.546 mmol, 1.0 equiv), 5-amino-2-(4-isopropylpiperazin-1-yl)benzonitrile (200 mg, 0.819 mmol, 1.5 equiv), and PTSA monohydrate (208 mg, 1.09 mmol, 2.0 equiv) in IPA (5 mL) was heated to reflux for 2 days. After cooling to ambient temperature, the crude mixture was concentrated to dryness and taken in water, EtOAc, and 1N NaOH. The layers were separated. The organic layer was washed with 1N NaOH 1×, dried over Na2SO4, filtered, and concentrated to dryness. The crude product was purified by flash chromatography and eluted with DCM:2M NH3/MeOH=100:0 to 95:5 using 1% 2M NH3/MeOH increments to give Compound 138 (195 mg, 71% yield) as a solid.

後処理

  1. temperaturewas heated
  2. temperatureto reflux for 2 days
  3. concentrationthe crude mixture was concentrated to dryness
  4. customThe layers were separated
  5. washThe organic layer was washed with 1N NaOH 1×
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe crude product was purified by flash chromatography
  10. washeluted with DCM

出典と根拠

ORDレコード
ord-d8c98ba4ec104a079b04b571468b3b11
出典データセット
uspto-grants-2016_04
特許番号
US09321763B2

反応ノート

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