Lithium Hydroxide → HCID 90042710, compound

HRID 929191Notes

Reaction equation

HRID 929191 reaction equation
[Li+].[OH-].Br[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:15]=[C:14]3[N:16]=[C:17]([O:19][C@H:20]4[C@H:24]5[O:25][CH2:26][C@@H:27]([OH:28])[C@H:23]5[O:22][CH2:21]4)[NH:18][C:13]3=[CH:12][C:11]=2[Cl:29])=[CH:6][CH:5]=1.[C:30]([C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1)(=[O:32])[CH3:31]>O1CCOCC1.O>[OH:28][C@@H:27]1[CH2:26][O:25][C@@H:24]2[C@H:20]([O:19][C:17]3[NH:18][C:13]4[C:14]([N:16]=3)=[N:15][C:10]([C:7]3[CH:8]=[CH:9][C:4]([C:36]5[CH:37]=[CH:38][C:33]([C:30](=[O:32])[CH3:31])=[CH:34][CH:35]=5)=[CH:5][CH:6]=3)=[C:11]([Cl:29])[CH:12]=4)[CH2:21][O:22][C@H:23]12

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 37021224-Acetylphenylboronic acidHCID 68282650HCID 68282650, compound

Product 1

HCID 90042710HCID 90042710, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

LiOH (0.41 ml, 1.230 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (41.8 mg, 0.051 mmol) were added to a stirred solution of (3R,3aR,6R,6aR)-6-[[5-(4-bromophenyl)-6-chloro-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol (225.2 mg, 0.497 mmol) and 4-acetylphenylboronic acid (100.3 mg, 0.612 mmol) in dioxane (4.0 ml) and water (0.59 ml). The reaction mixture was degassed (3×) and placed under nitrogen before being heated to 80° C. for 18 h. The reaction mixture was then partitioned between EtOAc (50 ml) and water (50 ml). The aqueous layer was extracted with EtOAc (2×50 ml). The organic layers were combined, washed with brine (1×50 ml), dried over Na2SO4, filtered, and evaporated under reduced pressure to give a yellow solid. The solid was purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-100% acetonitrile/water+0.05% TFA gradient followed by a 100% acetonitrile+0.05% TFA flush. The desired fractions were combined, evaporated under reduced pressure, and lyophilized from ethanol and benzene to give the title compound as a light yellow solid. LC-MS: calculated for C26H22ClN3O5 491.12 observed m/e: 492.10 (M+H)+ (Rt 1.14/2 min); 1H NMR δ (ppm) (CD3OD): 8.11 (d, J=8.5 Hz, 2H), 7.85 (d, J=8.5 Hz, 2H), 7.83 (s, 1H), 7.77-7.82 (m, 4H), 5.55 (qt, J=5 Hz, 1H), 4.97 (t, J=5.3 Hz, 1H), 4.47 (t, J=4.8, 1H), 4.27-4.30 (m, 1H), 4.17 (dd, J=5.8, J=10.3, 1H), 4.11 (dd, J=4.8 Hz, J=10.3, 1H), 3.90 (t, J=7.5 Hz, 1H), 3.60 (t, J=8.8 Hz, 1H) 2.65 (s, 3H).

Workup

  1. customThe reaction mixture was degassed (3×)
  2. customThe reaction mixture was then partitioned between EtOAc (50 ml) and water (50 ml)
  3. extractionThe aqueous layer was extracted with EtOAc (2×50 ml)
  4. washwashed with brine (1×50 ml)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customto give a yellow solid
  9. customThe solid was purified by preparative HPLC reverse phase (C-18)
  10. washeluting with a 20%-100% acetonitrile/water+0.05% TFA
  11. customflush
  12. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-83829400e00b4530bff85d3797e666fa
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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