Potassium Carbonate → 2-[5-fluoro-2-(hydroxymethyl)-3-[7-[[5-[4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-3H-benzimidazol-5-yl]phenyl]-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1-one

HRID 1024073ノート

反応式

HRID 1024073 の反応式
Cl[C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH:24]4[CH2:27][O:26][CH2:25]4)[CH2:20][CH2:19]3)=[CH:14][N:13]=2)[C:5]2[N:9]=[CH:8][NH:7][C:6]=2[CH:10]=1.C([O:31][CH2:32][C:33]1[C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37][C:36]([F:48])=[CH:35][C:34]=1[N:49]1[CH2:61][CH2:60][N:52]2[C:53]3[CH2:54][CH2:55][CH2:56][CH2:57][C:58]=3[CH:59]=[C:51]2[C:50]1=[O:62])(=O)C.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1.O>[F:48][C:36]1[CH:37]=[C:38]([C:2]2[CH:3]=[C:4]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:19][CH2:20][N:21]([CH:24]5[CH2:27][O:26][CH2:25]5)[CH2:22][CH2:23]4)=[CH:14][N:13]=3)[C:5]3[N:9]=[CH:8][NH:7][C:6]=3[CH:10]=2)[C:33]([CH2:32][OH:31])=[C:34]([N:49]2[CH2:61][CH2:60][N:52]3[C:53]4[CH2:54][CH2:55][CH2:56][CH2:57][C:58]=4[CH:59]=[C:51]3[C:50]2=[O:62])[CH:35]=1

参加物

8

反応物 4

HCID 11430Potassium CarbonateHCID 75806TricyclohexylphosphineHCID 580442052-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl AcetateHCID 866841506-Chloro-N-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)-1H-benzo[d]imidazol-4-amine

生成物 1

HCID 715573032-[5-fluoro-2-(hydroxymethyl)-3-[7-[[5-[4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-3H-benzimidazol-5-yl]phenyl]-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1-one収率 10.1%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

A microwave vial equipped with a magnetic stirrer was charged with 116c (300 mg, 0.78 mmol), 4-fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate 101k (545 mg, 1.13 mmol), potassium carbonate (414 mg, 3.0 mmol), tris(dibenzylideneacetone)dipalladium(0) (68 mg, 0.075 mmol), tricyclohexyl phosphine (210 mg, 0.75 mmol), water (0.2 mL), and dioxane (10 mL). After bubbling nitrogen through the suspension for 10 minutes, the sealed vial was heated at 110° C. overnight. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 116 as a white solid (52 mg, 10%). MS-ESI: [M+H]+ 663.3. 1H NMR (500 MHz, DMSO) δ 8.23 (bs, 1H), 8.11 (s, 1H), 7.88 (d, J=4.5 Hz, 1H), 7.35-7.31 (m, 1H), 7.23-7.17 (m, 2H), 7.13-7.09 (m, 2H), 6.52 (s, 1H), 4.57-4.45 (m, overlap, 4H), 4.31 (d, J=7.5 Hz, 2H), 4.11-4.01 (m, 4H), 3.51-3.47 (m, 1H), 3.10-3.06 (m, 4H), 2.59-2.41 (m, 8H), 1.81-1.68 (m, 4H)

後処理

  1. customA microwave vial equipped with a magnetic stirrer
  2. customAfter bubbling nitrogen through the suspension for 10 minutes
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by reverse-phase prep-HPLC

出典と根拠

ORDレコード
ord-0a8b608811f441d4b9b3dc69e99f0e1f
出典データセット
uspto-grants-2014_05
特許番号
US08722676B2

反応ノート

読み込み中…