Nitrogen → 3-(4-(6-chloro-2-(((3R,3aR,6R,6aR)-6-hydroxyhexahydrofuro[3,2-b]furan-3-yl)oxy)-1H-imidazo[4,5-b]pyridin-5-yl)phenyl)-3-methylthietane 1,1-dioxide

HRID 929262ノート

反応式

HRID 929262 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]2[NH:11][C:10]([O:12][C@H:13]3[C@H:17]4[O:18][CH2:19][C@@H:20]([OH:21])[C@H:16]4[O:15][CH2:14]3)=[N:9][C:5]2=[N:6][C:7]=1I.[Li+].[OH-].N#N.[CH3:26][C:27]1([C:33]2[CH:38]=[CH:37][C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][CH:34]=2)[CH2:30][S:29](=[O:32])(=[O:31])[CH2:28]1>O1CCOCC1.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].C(Cl)Cl.O>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:11][C:10]([O:12][C@@H:13]3[CH2:14][O:15][C@@H:16]4[C@H:20]([OH:21])[CH2:19][O:18][C@H:17]34)=[N:9][C:5]2=[N:6][C:7]=1[C:36]1[CH:35]=[CH:34][C:33]([C:27]2([CH3:26])[CH2:28][S:29](=[O:32])(=[O:31])[CH2:30]2)=[CH:38][CH:37]=1

参加物

8

反応物 4

HCID 947NitrogenHCID 3939Lithium HydroxideHCID 90042050(3R,3aR,6R,6aR)-6-((6-chloro-5-iodo-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-olHCID 900421873-Methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)thietane 1,1-dioxide

生成物 1

HCID 900674373-(4-(6-chloro-2-(((3R,3aR,6R,6aR)-6-hydroxyhexahydrofuro[3,2-b]furan-3-yl)oxy)-1H-imidazo[4,5-b]pyridin-5-yl)phenyl)-3-methylthietane 1,1-dioxide

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

Step E A solution of (3R,3aR,6R,6aR)-6-((6-chloro-5-iodo-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol (100 mg, 0.236 mmol), LiOH (29.7 mg, 0.708 mmol), and PdCl2(dppf)-CH2Cl2 adduct (38.6 mg, 0.047 mmol), in a thick-walled tube, was flushed with N2. Then water (0.5 ml) was added, followed by a solution of 3-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)thietane 1,1-dioxide (114 mg, from Step D) in dioxane (3.5 ml). The tube was flushed with N2, and placed in a preheated 72° C. hot oil bath and heated to 80° C. for 3 hours. The reaction mixture was cooled to RT and diluted with EtOAc (30 ml) and water (20 ml). The aqueous layer was separated, and extracted with EtOAc (25 ml). The combined organic layers were dried (Na2SO4), filtered and concentrated. The resulting crude material was purified by Isco™ system, 24 g gold cartridge, 30 ml flow rate, gradient —40/60 (1 min) to 100/0 (15 min) to 100/0 (19 min total run time) of EtOAc/hexanes. The fractions containing product were combined and concentrated to obtain the title compound as an off-white solid. LC-MS: observed m/e: 492.37 (M+H)+ (Rt 0.85/2 min)

後処理

  1. customThe tube was flushed with N2
  2. customplaced in a preheated 72° C.
  3. temperatureThe reaction mixture was cooled to RT
  4. additiondiluted with EtOAc (30 ml) and water (20 ml)
  5. customThe aqueous layer was separated
  6. extractionextracted with EtOAc (25 ml)
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting crude material was purified by Isco™ system, 24 g gold cartridge, 30 ml flow rate, gradient —40/60 (1 min) to 100/0 (15 min) to 100/0 (19 min total run time) of EtOAc/hexanes
  11. additionThe fractions containing product
  12. concentrationconcentrated

出典と根拠

ORDレコード
ord-f03657fe3b5941ddbb0751bcfb73adc6
出典データセット
uspto-grants-2016_03
特許番号
US09290517B2

反応ノート

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