Methanol → HCID 90067167, compound

HRID 929230Notes

Reaction equation

HRID 929230 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[NH:22][C:21]([O:23][C@@H:24]3[CH2:28][O:27][C@@H:26]4[C:29](=O)[CH2:30][O:31][C@H:25]34)=[N:20][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][CH:9]=1.[C:33](=[O:36])([O-])[O-].[NH4+:37].[NH4+:38].[C-]#N.[K+].[CH3:42][OH:43]>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:22][C:21]([O:23][C@@H:24]3[CH2:28][O:27][C@@H:26]4[C:29]5([CH2:30][O:31][C@H:25]34)[NH:38][C:42](=[O:43])[NH:37][C:33]5=[O:36])=[N:20][C:5]2=[N:6][C:7]=1[C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 9032Potassium CyanideHCID 517111Ammonium CarbonateHCID 90041963HCID 90041963, compound

Product 1

HCID 90067167HCID 90067167, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of (3R,3aR,6aS)-3-[[6-chloro-5-(4-phenylphenyl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,6a-tetrahydrofuro[3,2-b]furan-6-one (91 mg, 0.203 mmol), ammonium carbonate (39.0 mg, 0.406 mmol) and potassium cyanide (14.6 mg, 0.224 mmol) in methanol (0.4 ml) was stirred at room temperature for 22 hours. The mixture was placed in a 40 degree oil bath for an additional 23 hours. Then the reaction mixture was partitioned between ethyl acetate (30 mL) and water (20 mL), washed with brine (1×5 mL), MgSO4, filtered and evaporated to give a residue. The residue was dissolved in dimethylsulfoxide and purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-80% acetonitrile/water to give the title compound. LC-MS: calculated for C26H20ClN5O5 517.12 observed m/e: 518.19 (M+H)+ (Rt 1.17/2 min); 1H NMR δ (ppm) (CD3OD): 7.94 (s, 1H), 7.76 (ABq, 4H), 7.71 (d, 2H), 7.48 (dd, 2H), 7.39 (dd, 1H), 5.64 (m, 1H), 5.18 (t, 1H), 4.58 (d, 1H), 4.26 (dd, 2H), 4.19 (dd, 1H), 4.11 (d, 1H) and 3.95 (d, 1H).

Workup

  1. customwas placed in a 40 degree
  2. customfor an additional 23 hours
  3. customThen the reaction mixture was partitioned between ethyl acetate (30 mL) and water (20 mL)
  4. washwashed with brine (1×5 mL), MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto give a residue
  8. custompurified by preparative HPLC reverse phase (C-18)
  9. washeluting with a 20%-80% acetonitrile/water

Sources & evidence

ORD record
ord-eea843bf1a9148ab8fcc18ee24d77d8a
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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