Ethanol → HCID 178465313, compound

HRID 447256Notes

Reaction equation

HRID 447256 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, J7.2 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-fcb1b628677a4cba8850c0362c7aee57
Source dataset
uspto-grants-2013_07
Patent number
US08481551B2

Reaction notes

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