Diisopropylethylamine → (S)-3-fluoro-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzonitrile

HRID 716227ノート

反応式

HRID 716227 の反応式
O[CH2:2][C:3]1[CH:12]=[N:11][C:10]2[N:9]3[CH2:13][CH2:14][CH2:15][C@H:8]3[C:7](=[O:16])[NH:6][C:5]=2[CH:4]=1.[F:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)[C:21]#[N:22].[I-].C(C[P+](C)(C)C)#N.C(N(CC)C(C)C)(C)C>C(#N)CC.CS(C)=O>[F:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[N:26]1[CH2:31][CH2:30][N:29]([CH2:2][C:3]2[CH:12]=[N:11][C:10]3[N:9]4[CH2:13][CH2:14][CH2:15][C@H:8]4[C:7](=[O:16])[NH:6][C:5]=3[CH:4]=2)[CH2:28][CH2:27]1)[C:21]#[N:22]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 5961133-Fluoro-4-piperazin-1-yl-benzonitrileHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 58324378(S)-3-(hydroxymethyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-one

生成物 1

HCID 46864918(S)-3-fluoro-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzonitrile収率 21.65%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 7854Propionitrile溶媒

反応条件

温度
90 °C

実験手順

(S)-3-(hydroxymethyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-one (150 mg, 0.684 mmol), 3-fluoro-4-(piperazin-1-yl)benzonitrile (140 mg, 0.684 mmol), (cyanomethyl)trimethylphosphonium iodide (249 mg, 1.026 mmol) and N,N-diisopropylethylamine (0.597 ml, 3.42 mmol) were suspended in propionitrile (2 ml) and heated in a closed vial at 90° C. for 2 h. The reaction mixture became a clear dark brown solution. It was cooled to room temperature, diluted with DMSO (2 mL) and purified using preparative HPLC (25-95% acetonitrile in water, NH4HCO3 buffered). The fractions containing product were concentrated in vacuo and crystallized with water (3 mL). The precipitate was filtered and dried in vacuum to afford (S)-3-fluoro-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzonitrile (60.2 mg, 0.148 mmol, 21.65% yield) as a light brown solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 1.83-2.03 (m, 3H) 2.11-2.24 (m, 1H) 2.44-2.49 (m, 4H) 3.07-3.22 (m, 4H) 3.34-3.42 (m, 3H) 3.53-3.65 (m, 1H) 3.93-4.03 (m, 1H) 6.97 (d, J=2.02 Hz, 1H) 7.11 (t, J=8.72 Hz, 1H) 7.56 (dd, J=8.46, 1.64 Hz, 1H) 7.61 (d, J=2.02 Hz, 1H) 7.69 (dd, J=13.39, 2.02 Hz, 1H) 10.44 (s, 1H); [M+H] calc'd for C22H23FN6O, 407. found, 407; melting point 226° C.

後処理

  1. temperatureIt was cooled to room temperature
  2. custompurified
  3. additionThe fractions containing product
  4. concentrationwere concentrated in vacuo
  5. customcrystallized with water (3 mL)
  6. filtrationThe precipitate was filtered
  7. customdried in vacuum

出典と根拠

ORDレコード
ord-95e2bc90d2b347b59b919fff33474729
出典データセット
uspto-grants-2015_11
特許番号
US09187497B2

反応ノート

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