Dichlorobis(triphenylphosphine)palladium → Palladium

HRID 1972310노트

반응식

HRID 1972310 반응식
[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[N:11]=[C:12]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)[C:13]4[CH:18]=[C:17]([CH2:19][N:20]5[CH2:25][CH2:24][N:23]([S:26]([CH3:29])(=[O:28])=[O:27])[CH2:22][CH2:21]5)[S:16][C:14]=4[N:15]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1.ClC1N=C(N2CCOCC2)C2C=C(CN3CCN(S(C)(=O)=O)CC3)SC=2N=1.[O:63]1[CH2:68][CH2:67][CH2:66][CH2:65][CH:64]1N1C=C2C(C=CC=C2B2OC(C)(C)C(C)(C)O2)=N1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd:126]Cl>O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>[CH3:29][S:26]([N:23]1[CH2:24][CH2:25][N:20]([CH2:19][C:17]2[S:16][C:14]3[N:15]=[C:10]([C:5]4[C:4]5[C:9]([CH:8]=[CH:7][CH:6]=4)=[N:1][N:2]([CH:64]4[CH2:65][CH2:66][CH2:67][CH2:68][O:63]4)[CH:3]=5)[N:11]=[C:12]([N:30]4[CH2:31][CH2:32][O:33][CH2:34][CH2:35]4)[C:13]=3[CH:18]=2)[CH2:21][CH2:22]1)(=[O:27])=[O:28].[Pd:126]

참가 물질

8

반응물 4

HCID 6102075Dichlorobis(triphenylphosphine)palladiumHCID 252532304-(2-(1H-indazol-4-yl)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[2,3-d]pyrimidin-4-yl)morpholineHCID 252688432-(Tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazoleHCID 568339462-Chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinothieno[2,3-d]pyrimidine

생성물 2

HCID 23938PalladiumHCID 252691944-(6-((4-(Methylsulfonyl)piperazin-1-yl)methyl)-2-(2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl)thieno[2,3-d]pyrimidin-4-yl)morpholine

시약·촉매·용매 2

HCID 10340Sodium Carbonate용매HCID 312751,4-Dioxane용매

반응 조건

온도
88 °C

실험 절차

Scheme 8 shows the synthesis of 4-(2-(1H-Indazol-4-yl)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[2,3-d]pyrimidin-4-yl)morpholine II sulfate salt starting with Suzuki coupling of 4-(2-chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[2,3-d]pyrimidin-4-yl)morpholine 20 in 1,4-dioxane with 2-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole 10 (1.25 equiv.) and bis(triphenylphosphine)palladium (II) chloride (0.02 equiv.) in aqueous sodium carbonate. The mixture was heated to 88° C. and stirred for 14 hours. The reaction mixture was cooled, filtered, rinsed with water, and stirred with FLORISIL® (60-100 mesh, Sigma-Aldrich Chemical Company, Inc) in methylene chloride at ambient temperature for 5 hours. The mixture was filtered, rinsed with methylene chloride and ethyl acetate, and the filtrate and the rinse were combined and concentrated to give solid 21 with Pd content of 150 ppm. The solid was dissolved in methylene chloride and SILIABOND® Thiourea (Silicycle Inc) was added. The mixture was stirred for 5 hours, filtered, rinsed with methylene chloride and ethyl acetate. All the filtrate and the rinse were combined and concentrated to give 4-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-2-(2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl)thieno[2,3-d]pyrimidin-4-yl)morpholine 21 as a solid in 70% yield with Pd content<10 ppm), along with a minor amount of THP regioisomer 21A.

후처리

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered
  3. washrinsed with water
  4. stirringstirred with FLORISIL® (60-100 mesh, Sigma-Aldrich Chemical Company, Inc) in methylene chloride at ambient temperature for 5 hours
  5. filtrationThe mixture was filtered
  6. washrinsed with methylene chloride and ethyl acetate
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-36c0f470e6ab468d97035e87b766c204
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431694B1

반응 노트

불러오는 중…