Ethanol → HCID 178465313, compound

HRID 869107Notes

Reaction equation

HRID 869107 reaction equation
[P:1]([O:19][C:20]([C:23]1[N:28]=[CH:27][C:26]([C:29]2[C:43]([F:44])=[C:42]([C@H:45]3[CH2:49][CH2:48][CH2:47][O:46]3)[C:32]3[NH:33][C:34]([NH:36][C:37]([NH:39][CH2:40][CH3:41])=[O:38])=[N:35][C:31]=3[CH:30]=2)=[CH:25][N:24]=1)([CH3:22])[CH3:21])([O:11]CC1C=CC=CC=1)([O:3]CC1C=CC=CC=1)=[O:2].CCO.[OH-].[Na+:54]>[Pd].O>[P:1]([O-:11])([O-:3])([O:19][C:20]([C:23]1[N:28]=[CH:27][C:26]([C:29]2[C:43]([F:44])=[C:42]([C@H:45]3[CH2:49][CH2:48][CH2:47][O:46]3)[C:32]3[NH:33][C:34]([NH:36][C:37]([NH:39][CH2:40][CH3:41])=[O:38])=[N:35][C:31]=3[CH:30]=2)=[CH:25][N:24]=1)([CH3:21])[CH3:22])=[O:2].[Na+:54].[Na+:54]

Participants

6

Reactant 3

HCID 702EthanolHCID 14798Sodium HydroxideHCID 178465310HCID 178465310, compound

Product 1

HCID 178465313HCID 178465313, compoundYield 94.12%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
23 °C

Procedure

A 1 L round bottom flask was charged with (R)-dibenzyl 2-(5-(2-(3-ethylureido)-6-fluoro-7-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazol-5-yl)pyrimidin-2-yl)propan-2-yl phosphate (24) (9.37 g, 13.61 mmol), EtOH (300 mL), water (150 mL), Pd/C (10 wt % dry basis, wet, Degussa type, 3 g) and 1 M aqueous NaOH (27.22 mL, 27.22 mmol). The suspension was evacuated for 3 min (needle to pump) then placed under an atmosphere of hydrogen gas (balloon). After stirring 2.5 h at 23° C., the reaction was filtered through a 0.22 μm PES membrane (disposable Corning filter system, 1 L, polystyrene, #431098) to remove catalyst and washed with EtOH (50 mL). The resulting solution was concentrated, the residue dissolved in water (80 mL), treated with MeCN (80 mL), then frozen and lyophilized to give disodium (R)-2-(5-(2-(3-ethylureido)-6-fluoro-7-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazol-5-yl)pyrimidin-2-yl)propan-2-yl phosphate (W) (7.10 g, 12.81 mmol, 94.12%) as a white solid. ESMS (M+1)=509.3; 1H NMR (300 MHz, D2O) δ 8.58 (s, 2H), 6.92 (d, J=6.3 Hz, 1H), 5.13 (t, J=7.5 Hz, 1H), 3.98-3.81 (m, 2H), 3.04 (q, J=7.2 Hz, 2H), 2.26 (t, J=5.7 Hz, 1H), 1.97-1.92 (m, 2H), 1.67 (s, 6H) and 1.01 (t, J=7.2 Hz, 3H) ppm.

Workup

  1. customThe suspension was evacuated for 3 min (needle to pump)
  2. filtrationthe reaction was filtered through a 0.22 μm PES membrane (disposable Corning filter system, 1 L, polystyrene, #431098)
  3. customto remove catalyst
  4. washwashed with EtOH (50 mL)
  5. concentrationThe resulting solution was concentrated
  6. dissolutionthe residue dissolved in water (80 mL)
  7. additiontreated with MeCN (80 mL)
  8. temperaturefrozen

Sources & evidence

ORD record
ord-0367e2ff67314a5bbbd29056c620d613
Source dataset
uspto-grants-2015_03
Patent number
US08969359B2

Reaction notes

Loading…