Cesium carbonate → 2-({5-Chloro-2-[(1,3-dimethyl-1H-pyrazol-4-yl)-amino]-4-pyridinyl}amino)-N-(methyloxy)benzamide

HRID 62504

反応式

HRID 62504 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[CH:26]=[C:25]([NH2:27])[C:24]([CH3:28])=[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:27][C:25]2[C:24]([CH3:28])=[N:23][N:22]([CH3:21])[CH:26]=2)=[N:3][CH:4]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 44310561,3-dimethyl-1H-pyrazol-4-amineHCID 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide

生成物 1

HCID 446095112-({5-Chloro-2-[(1,3-dimethyl-1H-pyrazol-4-yl)-amino]-4-pyridinyl}amino)-N-(methyloxy)benzamide収率 18%

試薬・触媒・溶媒 2

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

反応条件

温度
140 °C

実験手順

A microwave tube was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide (250 mg, 0.8 mmol), 1,3-dimethyl-1H-pyrazol-4-amine (187 mg, 1.68 mmol), cesium carbonate (783 mg, 2.4 mmol) and dioxane/THF (3:1 ml). The reaction mixture was degassed under nitrogen for 10 min and palladium (II) acetate (9 mg, 0.04 mmol) and BINAP (50 mg, 0.08 mmol) were added. The mixture was stirred in a microwave at 140° C. for 40 min. It was evaporated and the residue dissolved in MeOH was filtered thru celite and thru an Acrodisc and purified further using preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid). Fractions were combined and evaporated. Ether was added to the residue and a tan precipitate crashed out. It was filtered off and dried under vacuum at 40° C. for 2 days to afford the desired product (55 mg, 18%) as a tan solid. LC-MS (ES) m/z=387.1, [M+H]+=389.1. 1H NMR (400 MHz, DMSO-d6) ppm 11.93 (br. s., 1 H) 9.51 (br. s., 1 H) 8.03 (s, 1 H) 7.96 (s, 1 H) 7.82 (s, 1 H) 7.51-7.61 (m, 3 H) 7.07-7.15 (m, 1 H) 6.68 (s, 1 H) 3.70 (d, J=4.29 Hz, 6 H) 2.07 (s, 3 H).

後処理

  1. customThe reaction mixture was degassed under nitrogen for 10 min
  2. customIt was evaporated
  3. dissolutionthe residue dissolved in MeOH
  4. filtrationwas filtered thru celite
  5. custompurified further
  6. customevaporated
  7. additionEther was added to the residue
  8. filtrationIt was filtered off
  9. customdried under vacuum at 40° C. for 2 days

出典と根拠

ORDレコード
ord-582df86190044f2abe427c196f524eaf
出典データセット
uspto-grants-2016_09
特許番号
US09446034B2

関連ノート

読み込み中…