Potassium Carbonate → HCID 118413234, compound

HRID 929244Notes

Reaction equation

HRID 929244 reaction equation
CB(O)O.[N:5]1([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][C:19]([C:22]4[N:27]=[C:26]5[N:28]=[C:29]([O:31][C@H:32]6[C@H:36]7[O:37][CH2:38][C@@H:39]([OH:40])[C@H:35]7[O:34][CH2:33]6)[NH:30][C:25]5=[CH:24][C:23]=4Cl)=[CH:18][CH:17]=3)=[CH:12][CH:11]=2)[CH:9]=[N:8][CH:7]=[N:6]1.[C:42](=O)([O-])[O-].[K+].[K+]>[Pd+2].O1CCOCC1>[N:5]1([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][C:19]([C:22]4[N:27]=[C:26]5[N:28]=[C:29]([O:31][C@H:32]6[C@H:36]7[O:37][CH2:38][C@@H:39]([OH:40])[C@H:35]7[O:34][CH2:33]6)[NH:30][C:25]5=[CH:24][C:23]=4[CH3:42])=[CH:18][CH:17]=3)=[CH:12][CH:11]=2)[CH:9]=[N:8][CH:7]=[N:6]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 139377Methylboronic AcidHCID 60171877(3R,3aR,6R,6aR)-6-[[6-chloro-5-[4-[4-(1,2,4-triazol-1-yl)phenyl]phenyl]-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol

Product 1

HCID 118413234HCID 118413234, compound

Reagents, catalysts & solvents 2

HCID 105144Allyl(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)chloropalladium(II)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

Methyl boronic acid (174 mg, 2.90 mmol), (3R,3aR,6R,6aR)-6-((5-(4′-(1H-1,2,4-triazol-1-yl)-[1,1′-biphenyl]-4-yl)-6-chloro-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol (150 mg, 0.290 mmol) and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl)]palladium(II) (86 mg, 0.116 mmol) were added as solids to a microwave tube, followed by degassed 1,4-dioxane (2 mL) and 2 M aqueous potassium carbonate (1741 uL, 3.48 mmol). The tube was sealed and heated to 140° C. in a microwave for 30 minutes. The organic phase of the reaction was removed and evaporated under reduced pressure. The crude mixture was diluted in DMSO (2 mL) and purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 5%-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 water/acetonitrile to give the title compound as white solid. LC-MS: calculated for C22H24N6O4 496.19 observed m/e: 497.24 (M+H)+ (Rt 0.79/2.5 min); 1H NMR δ (ppm) ((CD3)2SO):

Workup

  1. customThe tube was sealed
  2. customThe organic phase of the reaction was removed
  3. customevaporated under reduced pressure
  4. additionThe crude mixture was diluted in DMSO (2 mL)
  5. custompurified by preparative HPLC reverse phase (C-18)
  6. washeluting with a 5%-100% acetonitrile/water+0.05% TFA
  7. customflush
  8. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-12c5c21b0d884ea381a8a1c8e9901f98
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

Loading…