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

HRID 2264607노트

반응식

HRID 2264607 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

반응 조건

온도
70 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-531bff4363e6453cb220043f494e27ab
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07855215B2

반응 노트

불러오는 중…