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Dichloromethane → (6-Amino-3-aza-bicyclo[3.1.0]hex-3-yl)-(4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-methanone

HRID 425904
ノート
印刷プレビュー

反応式

HRID 425904 の反応式
C(OC(=O)[NH:7][CH:8]1[CH:13]2[CH:9]1[CH2:10][N:11]([C:14](=[O:22])[C:15]1[CH:20]=[CH:19][C:18](I)=[CH:17][CH:16]=1)[CH2:12]2)(C)(C)C.[Cl:24][C:25]1[C:30]([F:31])=[CH:29][CH:28]=[C:27]([Cl:32])[C:26]=1[CH:33]([O:35][C:36]1[C:37]([NH2:51])=[N:38][CH:39]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH:41]=1)[CH3:34].C(Cl)Cl.C([O-])([O-])=O.[Cs+].[Cs+].Cl.O1CCOCC1>COCCOC.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:7][CH:8]1[CH:9]2[CH:13]1[CH2:12][N:11]([C:14]([C:15]1[CH:16]=[CH:17][C:18]([C:40]3[CH:39]=[N:38][C:37]([NH2:51])=[C:36]([O:35][CH:33]([C:26]4[C:27]([Cl:32])=[CH:28][CH:29]=[C:30]([F:31])[C:25]=4[Cl:24])[CH3:34])[CH:41]=3)=[CH:19][CH:20]=1)=[O:22])[CH2:10]2
参加物実験手順後処理出典と根拠反応ノート

参加物

9

反応物 5

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 204431481,4-Dioxane hydrochlorideHCID 211113943-(1-(2,6-Dichloro-3-fluorophenyl)ethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 58886163[3-(4-Iodo-benzoyl)-3-aza-bicyclo[3.1.0]hex-6-yl]-carbamic acid tert-butyl ester

生成物 1

HCID 21111335
(6-Amino-3-aza-bicyclo[3.1.0]hex-3-yl)-(4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-methanone
収率 26%

試薬・触媒・溶媒 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 80711,2-Dimethoxyethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a mixture of [3-(4-iodo-benzoyl)-3-aza-bicyclo[3.1.0]hex-6-yl]-carbamic acid tert-butyl ester (100 mg, 0.234 mmol) and 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (100 mg, 0.234 mmol) in DME (2 mL) was added Pd(dppf)2Cl2.CH2Cl2 (10 mg, 0.012 mmol) and Cs2CO3 (351 mg, 0.702 mmol). The mixture was bubbled with nitrogen for 10 min then microwaved at 150° C. for 30 min. LCMS checked that the reaction was completed. The crude reaction mixture was diluted with ethyl acetate followed by washings with water and brine. The solution was dried over MgSO4. Purification by prep-HPLC afforded a solid. The solid was stirred with 4 N HCl/dioxane (3 mL) for 3 hr at room temperature. Removal of the volatiles led to a residue that was purified by prep-HPLC to afford (6-amino-3-aza-bicyclo[3.1.0]hex-3-yl)-(4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-methanone (30 mg, yield 26%).

後処理

  1. customThe mixture was bubbled with nitrogen for 10 min
  2. customthen microwaved at 150° C. for 30 min
  3. customThe crude reaction mixture
  4. washfollowed by washings with water and brine
  5. dry with materialThe solution was dried over MgSO4
  6. customPurification
  7. customby prep-HPLC afforded a solid
  8. customRemoval of the volatiles
  9. customwas purified by prep-HPLC

出典と根拠

ORDレコード
ord-b1868f8c33cc4b0e8aa3583a591db4a4
出典データセット
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08106197B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート