HCID 86695505, compound → (1R,2S)-1-(4-(6-(1-aminoethyl)pyridin-3-yl)phenyl)-2-(2,2-difluoroacetamido)-3-fluoropropyl dihydrogen phosphate

HRID 1487553Notes

Reaction equation

HRID 1487553 reaction equation
C([O:8][P:9]([O:19][C@H:20]([C:30]1[CH:35]=[CH:34][C:33]([C:36]2[CH:37]=[CH:38][C:39]([CH:42]([NH:44]C(=O)OCC3C=CC=CC=3)[CH3:43])=[N:40][CH:41]=2)=[CH:32][CH:31]=1)[C@H:21]([NH:24][C:25](=[O:29])[CH:26]([F:28])[F:27])[CH2:22][F:23])([O:11]CC1C=CC=CC=1)=[O:10])C1C=CC=CC=1>[Pd].C(O)C.O>[P:9]([OH:11])([OH:10])([O:19][C@H:20]([C:30]1[CH:31]=[CH:32][C:33]([C:36]2[CH:41]=[N:40][C:39]([CH:42]([NH2:44])[CH3:43])=[CH:38][CH:37]=2)=[CH:34][CH:35]=1)[C@H:21]([NH:24][C:25](=[O:29])[CH:26]([F:28])[F:27])[CH2:22][F:23])=[O:8]

Participants

5

Reactant 1

HCID 86695505HCID 86695505, compound

Product 1

HCID 71735455(1R,2S)-1-(4-(6-(1-aminoethyl)pyridin-3-yl)phenyl)-2-(2,2-difluoroacetamido)-3-fluoropropyl dihydrogen phosphateYield 91.4%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×

Procedure

Palladium on carbon (1:9, 23 mg, 0.022 mmol) is added to the product of step 4, Example 95A (235 mg, 0.308 mmol) in ethanol (5 mL) and water (1 mL). The mixture is evacuated with nitrogen three times and stirred under hydrogen for 5 hours. The reaction mixture is filtered through a 4 mL pad of solka flok and rinsed with alternating 4 mL rinses of ethanol and water ten times. The solvent is removed under reduced pressure to give the crude product, which is taken up in water (5 mL) and filtered through a 0.45 um filter disk, rinsing with water (2 mL). The filtrate is freeze dried to give the title product (126 mg): 1H NMR δ 8.75 (1H, s), 8.07 (1H, d), 7.63 (2H, d), 7.52-7.48 (4H, m), 6.00 (1H, t), 5.42 (1H, d), 4.82 (1H, dd), 4.64-4.43 (4H, m), 1.62 (3H, d); m/z: 447.12.

Workup

  1. customThe mixture is evacuated with nitrogen three times
  2. filtrationThe reaction mixture is filtered through a 4 mL pad of solka flok
  3. washrinsed
  4. customThe solvent is removed under reduced pressure
  5. customto give the crude product, which
  6. filtrationfiltered through a 0.45 um
  7. filtrationfilter disk
  8. washrinsing with water (2 mL)
  9. customdried

Sources & evidence

ORD record
ord-bd5332a7901c4103bbefdd1f86852ebd
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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