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Cesium carbonate → tert-Butyl (35)-4-(6-{[5-(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-3-(hydroxymethyl)pyridin-4-yl)-2-methoxypyridin-3-yl]amino}pyridin-3-yl)-3-methylpiperazine-1-carboxylate

HRID 593039
ノート
印刷プレビュー

反応式

HRID 593039 の反応式
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][C@@H:18]3[CH3:30])=[CH:13][CH:12]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C([O:34][CH2:35][C:36]1[C:37]([N:45]2[CH2:56][CH2:55][N:54]3[C:47](=[CH:48][C:49]4[CH2:50][C:51]([CH3:58])([CH3:57])[CH2:52][C:53]=43)[C:46]2=[O:59])=[N:38][CH:39]=[CH:40][C:41]=1B(O)O)(=O)C.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C([O-])([O-])=O.[Cs+].[Cs+].O.[OH-].[Li+]>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].O.O1CCOCC1>[CH3:57][C:51]1([CH3:58])[CH2:50][C:49]2[CH:48]=[C:47]3[N:54]([CH2:55][CH2:56][N:45]([C:37]4[C:36]([CH2:35][OH:34])=[C:41]([C:2]5[CH:3]=[C:4]([NH:10][C:11]6[N:16]=[CH:15][C:14]([N:17]7[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH2:19][C@@H:18]7[CH3:30])=[CH:13][CH:12]=6)[C:5]([O:8][CH3:9])=[N:6][CH:7]=5)[CH:40]=[CH:39][N:38]=4)[C:46]3=[O:59])[C:53]=2[CH2:52]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 5

HCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 168937Lithium hydroxide, monohydrateHCID 86684013tert-Butyl (3S)-4-{6-[(5-chloro-2-methoxypyridin-3-yl)amino]pyridin-3-yl}-3-methylpiperazine-1-carboxylateHCID 86684340[4-(Dihydroxyboranyl)-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl]methyl acetate

生成物 1

HCID 86726161tert-Butyl (35)-4-(6-{[5-(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-3-(hydroxymethyl)pyridin-4-yl)-2-methoxypyridin-3-yl]amino}pyridin-3-yl)-3-methylpiperazine-1-carboxylate収率 27.3%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒2 回HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 271a (650 mg, 1.50 mmol), {3-[(acetyloxy)methyl]-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-4-yl}boronic acid 199e (1.79 g, 4.5 mmol), Pd2(dba)3 (137.2 mg, 0.15 mmol), P(cy)3(167.4 mg, 0.60 mmol), Cs2CO3 (978 mg, 3.0 mmol), dioxane (20 mL), and water (0.5 mL). After three cycles of vacuum/argon flush, the mixture was heated at 110° C. for 16 h. After this time the reaction was cooled to room temperature. Lithium hydroxide monohydrate (1.89 g, 45 mmol) and water (2.0 mL) were added. The resulting mixture was stirred at 45° C. for 4 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 3:1 ethyl acetate/petroleum ether to afford 271b (290 mg, 27%) as a yellow solid. MS-ESI: [M+H]+ 709.3

後処理

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureAfter this time the reaction was cooled to room temperature
  4. filtrationIt was then filtered
  5. customthe filtrate was evaporated under reduced pressure
  6. customThe residue was purified by silica-gel column chromatography
  7. washeluting with 3:1 ethyl acetate/petroleum ether

出典と根拠

ORDレコード
ord-21151f0809684b419d540bb989cea8b9
出典データセット
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09238655B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート