Diisopropylethylamine → 6-(4-((6-Oxo-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[4,3-a]pyrido[3,2-e]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinonitrile

HRID 69680

反応式

HRID 69680 の反応式
O[CH2:2][C:3]1[CH:12]=[N:11][C:10]2[N:9]3[CH2:13][CH2:14][O:15][CH2:16][CH:8]3[C:7](=[O:17])[NH:6][C:5]=2[CH:4]=1.[I-].C(C[P+](C)(C)C)#N.C(N(C(C)C)C(C)C)C.[N:35]1([C:41]2[CH:48]=[CH:47][C:44]([C:45]#[N:46])=[CH:43][N:42]=2)[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1>C(#N)CC>[O:17]=[C:7]1[NH:6][C:5]2[CH:4]=[C:3]([CH2:2][N:38]3[CH2:39][CH2:40][N:35]([C:41]4[CH:48]=[CH:47][C:44]([C:45]#[N:46])=[CH:43][N:42]=4)[CH2:36][CH2:37]3)[CH:12]=[N:11][C:10]=2[N:9]2[CH2:13][CH2:14][O:15][CH2:16][CH:8]12

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 27371846-(Piperazin-1-yl)pyridine-3-carbonitrileHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 583243813-(hydroxymethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[4,3-a]pyrido[3,2-e]pyrazin-6(5H)-one

生成物 1

HCID 468645206-(4-((6-Oxo-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[4,3-a]pyrido[3,2-e]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinonitrile収率 60.1%

試薬・触媒・溶媒 1

HCID 7854Propionitrile溶媒

反応条件

温度
90 °C

実験手順

3-(hydroxymethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[4,3-a]pyrido[3,2-e]pyrazin-6(5H)-one (70.0 mg, 0.298 mmol) was suspended in propionitrile (0.74 mL) and (cyanomethyl)trimethylphosphonium iodide (87.0 mg, 0.357 mmol) was added followed by N-ethyl-N-isopropylpropan-2-amine (115 ul, 0.893 mmol). To the stirred mixture was then added 6-(piperazin-1-yl)nicotinonitrile (56.0 mg, 0.298 mmol). The reaction was heated to 90° C. with stirring for 16 h. The reaction was cooled to room temperature and left to sit 48 h. The precipitate was filtered off, washed with methanol (5 mL) and dried in vacuum to afford the title compound (72.5 mg, 60.1%) as a white solid. 1H NMR (CHLOROFORM-d) δ: 8.41 (d, J=1.8 Hz, 1H), 8.20 (br. s., 1H), 7.80 (d, J=2.0 Hz, 1H), 7.61 (dd, J=9.0, 2.4 Hz, 1H), 6.99 (br. s., 1H), 6.59 (d, J=9.1 Hz, 1H), 4.42 (dd, J=11.5, 3.7 Hz, 1H), 4.26 (dd, J=13.3, 1.6 Hz, 1H), 3.95-4.12 (m, 2H), 3.58-3.80 (m, 6H), 3.45 (s, 2H), 2.92-3.08 (m, 1H), 2.53 (br. s., 4H). [M+H] calc'd for C21H23N7O2, 406; found, 406.

後処理

  1. temperatureThe reaction was cooled to room temperature
  2. waitleft
  3. waitto sit 48 h
  4. filtrationThe precipitate was filtered off
  5. washwashed with methanol (5 mL)
  6. customdried in vacuum

出典と根拠

ORDレコード
ord-7ae7221a8aff43c29ae6c87c93ba4750
出典データセット
uspto-grants-2014_09
特許番号
US08822470B2

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