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2-(4-(Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ol → (2R,3 S,5R)-5-((6-chloro-5-(4'-(2-hydroxypropan-2-yl)-[1,1'-biphenyl]-4-yl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol

HRID 1050260
ノート
印刷プレビュー

反応式

HRID 1050260 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([C:15]([OH:18])([CH3:17])[CH3:16])=[CH:11][CH:10]=2)O1.Br[C:21]1[CH:26]=[CH:25][C:24]([C:27]2[N:32]=[C:31]3[N:33]=[C:34]([O:36][C@H:37]4[CH2:42][O:41][C@H:40]([CH2:43][OH:44])[C@@H:39]([OH:45])[CH2:38]4)[NH:35][C:30]3=[CH:29][C:28]=2[Cl:46])=[CH:23][CH:22]=1>O1CCOCC1.O.CCOC(C)=O.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]>[Cl:46][C:28]1[CH:29]=[C:30]2[NH:35][C:34]([O:36][C@H:37]3[CH2:42][O:41][C@H:40]([CH2:43][OH:44])[C@@H:39]([OH:45])[CH2:38]3)=[N:33][C:31]2=[N:32][C:27]=1[C:24]1[CH:25]=[CH:26][C:21]([C:9]2[CH:10]=[CH:11][C:12]([C:15]([OH:18])([CH3:16])[CH3:17])=[CH:13][CH:14]=2)=[CH:22][CH:23]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 2

HCID 591660132-(4-(Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-olHCID 90044340(2R,3 S,5R)-5-((5-(4-bromophenyl)-6-chloro-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)-tetrahydro-2H-pyran-3-ol

生成物 1

HCID 73332558(2R,3 S,5R)-5-((6-chloro-5-(4'-(2-hydroxypropan-2-yl)-[1,1'-biphenyl]-4-yl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol

試薬・触媒・溶媒 4

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
触媒
HCID 962Water溶媒2 回
HCID 8857Ethyl Acetate溶媒
HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ol (50.4 mg, 0.192 mmol) and (2R,3 S,5R)-5-((5-(4-bromophenyl)-6-chloro-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)-tetrahydro-2H-pyran-3-ol (70 mg, 0.154 mmol) were dissolved in dioxane (600 μl) and water (600 μl). The reaction mixture was sparged with N2 with 15 min and then [1,1′-Bis(Diphenylphosphino)-Ferrocene]Dichloropalladium (II) (22.53 mg, 0.031 mmol) was added. After stirring 3 h at 80° C., the reaction mixture was diluted with water and EtOAc. The aqueous phase was extracted with EtOAc (×2); and the combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. The resulting residue was purified by mass directed reverse phase HPLC eluted with acetonitrile in water containing 0.1% formic acid. The desired fractions were combined and lyophilized to give the title compound as a white solid. LC-MS: calculated for C27H28ClN3O5 509.17 observed m/e: 509.87 (M+H)+ (Rt 1.12/2 min); 1H NMR δ (ppm) (CD3OD): 7.82 (s, 1H), 7.72 (s, 4H), 7.66 (d, 2H), 7.59 (d, 2H), 5.11 (septet, 1H), 4.34 (dd, 1H), 3.88 (dd, 1H), 3.66-3.59 (m, 2H), 3.37 (t, 1H), 3.18-3.15 (m, 1H), 2.76-2.74 (m, 1H), 1.68 (q, 1H), 1.58 (s, 6H).

後処理

  1. customThe reaction mixture was sparged with N2 with 15 min
  2. extractionThe aqueous phase was extracted with EtOAc (×2)
  3. washand the combined extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by mass
  8. washeluted with acetonitrile in water containing 0.1% formic acid

出典と根拠

ORDレコード
ord-ec60823b1ccc407ea96067378c603a92
出典データセット
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09382243B2

反応ノート

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