Diisopropylethylamine → HCID 58324446、化合物

HRID 69600

反応式

HRID 69600 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:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=1[N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.[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:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=1[N:25]1[CH2:26][CH2:27][N:28]([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)[CH2:29][CH2:30]1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 27346371-(2,4-Difluorophenyl)piperazineHCID 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 58324446HCID 58324446、化合物収率 23.13%

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), 1-(2,4-difluorophenyl)piperazine (136 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 from water (3 mL). The precipitate was filtered and dried in vacuum to afford (S)-3-((4-(2,4-difluorophenyl)piperazin-1-yl)methyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-one (63.2 mg, 0.158 mmol, 23.13% yield) as a light brown solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 1.84-2.03 (m, 3 H) 2.09-2.26 (m, 1 H) 2.41-2.49 (m, 4 H) 2.88-2.99 (m, 4 H) 3.34-3.43 (m, 3 H) 3.54-3.63 (m, 1 H) 3.94-4.02 (m, 1 H) 6.93-7.09 (m, 3 H) 7.18 (ddd, J=12.44, 9.16, 2.91 Hz, 1 H) 7.61 (d, J=1.77 Hz, 1 H) 10.44 (s, 1 H); [M+H] calc'd for C21H23F2N5O, 400; found, 400.

後処理

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

出典と根拠

ORDレコード
ord-cc02f7ca5ad5464aae8b7c7f258a5875
出典データセット
uspto-grants-2014_09
特許番号
US08822470B2

関連ノート

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