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 929262Notes

Reaction equation

HRID 929262 reaction equation
[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

Participants

8

Reactant 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

Product 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

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

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)

Workup

  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

Sources & evidence

ORD record
ord-f03657fe3b5941ddbb0751bcfb73adc6
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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