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Cesium carbonate → 5-(2-(4-(Dimethylcarbamoyl)-2-methylphenylamino)-4-(tetrahydro-2H-pyran-4-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylpicolinamide

HRID 1487631
ノート
印刷プレビュー

反応式

HRID 1487631 の反応式
Cl[C:2]1[N:3]=[C:4]([O:29][CH:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[C:5]2[C:10]([C:11]3[CH:12]=[CH:13][C:14]([C:17]([NH:19][CH3:20])=[O:18])=[N:15][CH:16]=3)=[CH:9][N:8](COCC[Si](C)(C)C)[C:6]=2[N:7]=1.[NH2:36][C:37]1[CH:47]=[CH:46][C:40]([C:41]([N:43]([CH3:45])[CH3:44])=[O:42])=[CH:39][C:38]=1[CH3:48].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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>[CH3:44][N:43]([CH3:45])[C:41]([C:40]1[CH:46]=[CH:47][C:37]([NH:36][C:2]2[N:3]=[C:4]([O:29][CH:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:5]3[C:10]([C:11]4[CH:12]=[CH:13][C:14]([C:17]([NH:19][CH3:20])=[O:18])=[N:15][CH:16]=4)=[CH:9][NH:8][C:6]=3[N:7]=2)=[C:38]([CH3:48])[CH:39]=1)=[O:42]
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

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 167817704-amino-N,N,3-trimethylbenzamideHCID 867264585-(2-Chloro-4-(tetrahydro-2H-pyran-4-yloxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylpicolinamide

生成物 1

HCID 86726459
5-(2-(4-(Dimethylcarbamoyl)-2-methylphenylamino)-4-(tetrahydro-2H-pyran-4-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylpicolinamide
収率 21%

試薬・触媒・溶媒 2

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

反応条件

温度
150 °C

実験手順

5-(2-Chloro-4-(tetrahydro-2H-pyran-4-yloxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylpicolinamide (1 equiv), 4-amino-N,N,3-trimethylbenzamide (1 equiv), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.2 equiv), cesium carbonate (2 equiv), tris(dibenzylideneacetone)dipalladium(0) (0.1 equiv) and 1,4-dioxane (0.2 M) were combined in a microwave vial and irradiated heated at 150° C. for 30 min. The mixture was concentrated and purified by flash chromatography 0-55% (hexane:ethyl acetate—800 mL), followed by 5-15% B (DCM:MeOH—800 mL) in the same run. Fractions were combined, concentrated and the compound was deprotected according to General Procedure A. The reaction mixture was concentrated and purified to give the title compound (21% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.92 (d, J=1.95 Hz, 1H), 8.20 (dd, J=7.81, 1.56 Hz, 1H), 8.07 (dd, J=16.59, 8.39 Hz, 2H), 7.22-7.31 (m, 3H), 5.49 (s, 1H), 3.78-3.88 (m, 2H), 3.52-3.61 (m, 2H), 3.07 (s, 6H), 2.96 (s, 3H), 2.35 (s, 3H), 2.08 (d, J=13.28 Hz, 2H), 1.73-1.84 (m, 2H). MS (ESI) m/z 530.0 [M+1]+.

後処理

  1. customirradiated
  2. concentrationThe mixture was concentrated
  3. custompurified by flash chromatography 0-55% (hexane:ethyl acetate—800 mL)
  4. concentrationconcentrated
  5. concentrationThe reaction mixture was concentrated
  6. custompurified

出典と根拠

ORDレコード
ord-01ecd6fb67124e8dabfa741df4d55d45
出典データセット
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09428509B2

反応ノート

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