Water → 2-[3-(Hydroxymethyl)-4-[4-methyl-6-[[6-[4-(oxetan-3-yl)piperazin-1-yl]-3-pyridyl]amino]-5-oxo-pyrazin-2-yl]-2-pyridyl]-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1-one

HRID 1021906ノート

反応式

HRID 1021906 の反応式
C([O:4][CH2:5][C:6]1[C:7]([N:37]2[CH2:49][CH2:48][N:40]3[C:41]4[CH2:42][CH2:43][CH2:44][CH2:45][C:46]=4[CH:47]=[C:39]3[C:38]2=[O:50])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[N:13]=[C:14]([NH:20][C:21]2[CH:22]=[N:23][C:24]([N:27]3[CH2:32][CH2:31][N:30]([CH:33]4[CH2:36][O:35][CH2:34]4)[CH2:29][CH2:28]3)=[CH:25][CH:26]=2)[C:15](=[O:19])[N:16]([CH3:18])[CH:17]=1)(=O)C.[OH-].[Li+].O>C1COCC1.C(O)(C)C>[OH:4][CH2:5][C:6]1[C:7]([N:37]2[CH2:49][CH2:48][N:40]3[C:41]4[CH2:42][CH2:43][CH2:44][CH2:45][C:46]=4[CH:47]=[C:39]3[C:38]2=[O:50])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[N:13]=[C:14]([NH:20][C:21]2[CH:22]=[N:23][C:24]([N:27]3[CH2:28][CH2:29][N:30]([CH:33]4[CH2:36][O:35][CH2:34]4)[CH2:31][CH2:32]3)=[CH:25][CH:26]=2)[C:15](=[O:19])[N:16]([CH3:18])[CH:17]=1

参加物

6

反応物 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 86684366(4-(4-Methyl-6-(6-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-3-ylamino)-5-oxo-4,5-dihydropyrazin-2-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl Acetate

生成物 1

HCID 715576002-[3-(Hydroxymethyl)-4-[4-methyl-6-[[6-[4-(oxetan-3-yl)piperazin-1-yl]-3-pyridyl]amino]-5-oxo-pyrazin-2-yl]-2-pyridyl]-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1-one収率 30.8%

試薬・触媒・溶媒 2

HCID 3776Isopropanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

A mixture of 197f (200 mg, 0.30 mmol) and lithium hydroxide (70 mg, 3.0 mmol) in THF (9 mL), i-propanol (6 mL), and water (1 mL) was stirred at room temperature for 0.5 h. The mixture was concentrated under reduced pressure and diluted with water (4 mL). It was then extracted with dichloromethane (2×10 mL) and the combined dichloromethane extract was concentrated under reduced pressure. The residue was purified with reverse-phase prep-HPLC to afford 197 (59 mg, 30%) as yellow solid. MS-ESI: [M+H]+ 638. 1H NMR (500 MHz, DMSO-d6) δ 9.30 (s, 1H), 8.70 (d, J=2.5 Hz, 1H), 8.49 (d, J=5.5 Hz, 1H), 8.14-8.11 (m, 1H), 7.59 (s, 1H), 7.55 (d, J=5.0 Hz, 1H), 6.82 (d, J=9.5 Hz, 1H), 6.58 (s, 1H), 4.93 (t, J=5.5 Hz, 1H), 4.60-4.54 (m, 3H), 4.48-4.42 (m, 3H), 4.26-4.08 (m, 3H), 3.86 (d, J=12.0 Hz, 1H), 3.54 (s, 3H), 3.44-3.40 (m, overlap, 5H), 2.66-2.53 (m, 2H), 2.46-2.47 (m, 2H), 2.35-2.33 (m, 4H), 1.80-1.68 (m, 4H).

後処理

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additiondiluted with water (4 mL)
  3. extractionIt was then extracted with dichloromethane (2×10 mL)
  4. extractionthe combined dichloromethane extract
  5. concentrationwas concentrated under reduced pressure
  6. customThe residue was purified with reverse-phase prep-HPLC

出典と根拠

ORDレコード
ord-a6ee70f38b9140f5be543b1529ae41a2
出典データセット
uspto-grants-2014_05
特許番号
US08716274B2

反応ノート

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