Acetamide → [6-[[1-[[4-(4-Morpholinyl)-3-(trifluoromethyl)phenylamino]carbonyl]-1H-indol-5-yl]oxy]-4-pyrimidinyl]acetamide

HRID 2264607ノート

反応式

HRID 2264607 の反応式
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[N:14]([C:18]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:23]([C:33]([F:36])([F:35])[F:34])[CH:22]=2)=[O:19])[CH2:13][CH2:12]3)[CH:3]=1.[C:37]([NH2:40])(=[O:39])[CH3:38].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+]>O1CCOCC1.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]>[N:27]1([C:24]2[CH:25]=[CH:26][C:21]([NH:20][C:18]([N:14]3[C:15]4[C:11](=[CH:10][C:9]([O:8][C:4]5[N:5]=[CH:6][N:7]=[C:2]([CH2:38][C:37]([NH2:40])=[O:39])[CH:3]=5)=[CH:17][CH:16]=4)[CH:12]=[CH:13]3)=[O:19])=[CH:22][C:23]=2[C:33]([F:35])([F:36])[F:34])[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1

参加物

7

反応物 4

HCID 178AcetamideHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866182902,3-dihydro-5-(6-chloro-4-pyrimidinyloxy)-N-[4-(4-morpholinyl)-3-(trifluoromethyl)phenyl]-1H-indole-1-carboxamide

生成物 1

HCID 67531453[6-[[1-[[4-(4-Morpholinyl)-3-(trifluoromethyl)phenylamino]carbonyl]-1H-indol-5-yl]oxy]-4-pyrimidinyl]acetamide

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
70 °C

実験手順

A mixture of 2,3-dihydro-5-(6-chloro-4-pyrimidinyloxy)-N-[4-(4-morpholinyl)-3-(trifluoromethyl)phenyl]-1H-indole-1-carboxamide (Intermediate IIa; 1.30 g, 2.5 mmol), acetamide (0.22 g, 3.75 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis[diphenylphosphine] (90 mg, 0.15 mmol), tris(dibenzylideneacetone)dipalladium (45 mg, 0.05 mmol), caesium carbonate (1.14 g, 3.5 mmol) in dry dioxan (10 mL) is heated under an argon atmosphere at 70° C. for 15 h. The cooled suspension is filtered and the residue is dissolved in DMF (50 mL). The resulting solution is filtered (hyflo) and the solvent is evaporated off under reduced pressure to afford the crude product which is purified by preparative HPLC (VP Reprosil 100 Å-5 μm; eluent 0.1% TFA/H2O→0.09% TFA/CH3CN) and neutralised with saturated aqueous NaHCO3 to give the title compound as a colourless crystalline solid, m.p. 272-275° C.

後処理

  1. filtrationThe cooled suspension is filtered
  2. dissolutionthe residue is dissolved in DMF (50 mL)
  3. filtrationThe resulting solution is filtered (hyflo)
  4. customthe solvent is evaporated off under reduced pressure
  5. customto afford the crude product which
  6. customis purified by preparative HPLC (VP Reprosil 100 Å-5 μm; eluent 0.1% TFA/H2O→0.09% TFA/CH3CN)

出典と根拠

ORDレコード
ord-531bff4363e6453cb220043f494e27ab
出典データセット
uspto-grants-2010_12
特許番号
US07855215B2

反応ノート

読み込み中…