Cesium carbonate → 2-({5-Chloro-2-[(1,5-dimethyl-1H-pyrazol-4-yl)amino]-4-pyridinyl}amino)-N-(methyloxy)benzamide

HRID 62503

反応式

HRID 62503 の反応式
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][O:14][CH3:15])=[O:12])[C:5]([Cl:20])=[CH:4][N:3]=1.[CH3:21][N:22]1[C:26]([CH3:27])=[C:25]([NH2:28])[CH:24]=[N:23]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1.C1COCC1>[Cl:20][C:5]1[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][O:14][CH3:15])=[O:12])=[CH:7][C:2]([NH:28][C:25]2[CH:24]=[N:23][N:22]([CH3:21])[C:26]=2[CH3:27])=[N:3][CH:4]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 5738131,5-dimethyl-1H-pyrazol-4-amineHCID 634876Binap, (A+-)-HCID 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide

生成物 1

HCID 462150972-({5-Chloro-2-[(1,5-dimethyl-1H-pyrazol-4-yl)amino]-4-pyridinyl}amino)-N-(methyloxy)benzamide収率 7.3%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 22018518Dioxane tetrahydrofuran溶媒

反応条件

温度
150 °C

実験手順

A microwave tube was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide (200 mg, 0.64 mmol), 1,5-dimethyl-1H-pyrazol-4-amine (142 mg, 1.28 mmol), cesium carbonate (626 mg, 1.92 mmol) and dioxane/THF (3:1 ml). The reaction mixture was degassed under nitrogen for 10 min and palladium (II) acetate (5.8 mg, 0.03 mmol) and BINAP (40 mg, 0.06 mmol) were added. The tube was sealed and the mixture was stirred in an oil bath at 150° C. overnight. The dark brown solution was filtered thru celite and evaporated. It was dissolved in MeOH and filtered thru an Acrodisc (Pall Corporation; www.pall.com) and further purified on preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid). The dark brown oil residue was dissolved in DMF and water was slowly added. A tan precipitate crashed out and was filtered off and dried under vacuum at 40° C. for 2 hrs to afford the desired product (18 mg, 7.3%) as a tan solid. LC-MS [M+H]+=387.1, 389.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.91 (br. s., 1 H) 9.41 (br. s., 1 H) 7.85-7.98 (m, 2 H) 7.49-7.59 (m, 3 H) 7.42 (br. s., 1 H) 7.07-7.13 (m, 1 H) 6.50 (br. s., 1 H) 3.69 (d, J=10.36 Hz, 6 H) 2.11 (s, 3 H).

後処理

  1. customThe reaction mixture was degassed under nitrogen for 10 min
  2. customThe tube was sealed
  3. filtrationThe dark brown solution was filtered thru celite
  4. customevaporated
  5. dissolutionIt was dissolved in MeOH
  6. filtrationfiltered
  7. customfurther purified on preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid)
  8. dissolutionThe dark brown oil residue was dissolved in DMF
  9. additionwater was slowly added
  10. filtrationwas filtered off
  11. customdried under vacuum at 40° C. for 2 hrs

出典と根拠

ORDレコード
ord-ea7c1157f1984b9fbdb99776b1c61bea
出典データセット
uspto-grants-2016_09
特許番号
US09446034B2

関連ノート

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