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Cesium carbonate → GDC-0834 Racemate

HRID 888431
ノート
印刷プレビュー

反応式

HRID 888431 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[N:13]([CH3:14])[CH2:12][CH2:11][N:10]([CH3:15])[C:9]2=[O:16])=[CH:4][CH:3]=1.Br[C:18]1[C:19](=[O:44])[N:20]([CH3:43])[CH:21]=[C:22]([C:24]2[C:25]([CH3:42])=[C:26]([NH:30][C:31]([C:33]3[S:37][C:36]4[CH2:38][CH2:39][CH2:40][CH2:41][C:35]=4[CH:34]=3)=[O:32])[CH:27]=[CH:28][CH:29]=2)[N:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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>[CH3:14][N:13]1[CH2:12][CH2:11][N:10]([CH3:15])[C:9](=[O:16])[CH:8]1[C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:18]2[C:19](=[O:44])[N:20]([CH3:43])[CH:21]=[C:22]([C:24]3[C:25]([CH3:42])=[C:26]([NH:30][C:31]([C:33]4[S:37][C:36]5[CH2:38][CH2:39][CH2:40][CH2:41][C:35]=5[CH:34]=4)=[O:32])[CH:27]=[CH:28][CH:29]=3)[N:23]=2)=[CH:7][CH:6]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 576251203-(4-Aminophenyl)-1,4-dimethylpiperazin-2-oneHCID 57625151N-(3-(6-Bromo-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide

生成物 1

HCID 25235170GDC-0834 Racemate
収率 36.3%

試薬・触媒・溶媒 2

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

実験手順

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 4 (160 mg, 0.73 mmol), 11 (304 mg, 0.66 mmol), cesium carbonate (475 mg, 1.46 mmol) and 1,4-dioxane (10 mL). After bubbling nitrogen through the resulting solution for 30 minutes, Xantphos (32 mg, 0.056 mmol) and tris(dibenzylideneacetone)dipalladium(0) (30 mg, 0.033 mmol) were added and the reaction mixture was heated at reflux for 16 h. After this time the reaction was cooled to room temperature and concentrated under reduced pressure. The resulting residue was absorbed onto silica gel and purified by flash chromatography to give a residue, which was further purified by preparative reverse phase HPLC to afford a 30% yield (143 mg) of 12 as a yellow solid: mp 155-156° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.82 (s, 1H), 9.43 (s, 1H), 8.08 (d, 2H, J=7.5 Hz), 7.68 (s, 1H), 7.32 (d, 2H, J=7.5 Hz), 7.27-7.32 (m, 3H), 7.24 (s, 1H), 4.88 (bs, 1H), 3.42-3.75 (m, 4H), 3.59 (s, 3H), 2.95 (s, 3H), 2.76 (m, 2H), 2.61 (m, 5H), 2.28 (s, 3H), 1.78 (m, 4H); MS (ESI+) m/z 597 (M+H).

後処理

  1. customA 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. customAfter bubbling nitrogen through the resulting solution for 30 minutes
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 16 h
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was absorbed onto silica gel
  8. custompurified by flash chromatography
  9. customto give a residue, which
  10. customwas further purified by preparative reverse phase HPLC

出典と根拠

ORDレコード
ord-c8e47494dc81455d85e167a3fe2dbb05
出典データセット
uspto-grants-2012_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08247550B2

反応ノート

読み込み中…

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