Acetic Acid → (R)-N-((1S,2R,3S,4R)-4-{6-(2,2-Diphenyl-ethylamino)-2-[(R)-3-(3-pyridin-3-yl-ureido)-pyrrolidin-1-yl]-purin-9-yl}-2,3-dihydroxy-cyclopentyl)-2-hydroxy-propionamide

HRID 2382491Notes

Reaction equation

HRID 2382491 reaction equation
[C:1]1([CH:7]([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[CH2:8][NH:9][C:10]2[N:18]=[C:17]([N:19]3[CH2:23][CH2:22][C@@H:21]([NH:24][C:25]([NH:27][C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)=[O:26])[CH2:20]3)[N:16]=[C:15]3[C:11]=2[N:12]=[CH:13][N:14]3[C@@H:34]2[CH2:38][C@H:37]([NH:39][C:40](=[O:50])[C@H:41]([O:43]C3C=CC=CC=3)[CH3:42])[C@@H:36]([OH:51])[C@H:35]2[OH:52])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O)(=O)C>CCO.C1COCC1.[OH-].[Pd+2].[OH-]>[C:1]1([CH:7]([C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=2)[CH2:8][NH:9][C:10]2[N:18]=[C:17]([N:19]3[CH2:23][CH2:22][C@@H:21]([NH:24][C:25]([NH:27][C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)=[O:26])[CH2:20]3)[N:16]=[C:15]3[C:11]=2[N:12]=[CH:13][N:14]3[C@@H:34]2[CH2:38][C@H:37]([NH:39][C:40](=[O:50])[C@H:41]([OH:43])[CH3:42])[C@@H:36]([OH:51])[C@H:35]2[OH:52])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 2

HCID 176Acetic AcidHCID 66630509(R)-N-((1S,2R,3S,4R)-4-{6-(2,2-Diphenyl-ethylamino)-2-[(R)-3-(3-pyridin-3-yl-ureido)-pyrrolidin-1-yl]-purin-9-yl}-2,3-dihydroxy-cyclopentyl)-2-phenoxy-propionamide

Product 1

HCID 66631299(R)-N-((1S,2R,3S,4R)-4-{6-(2,2-Diphenyl-ethylamino)-2-[(R)-3-(3-pyridin-3-yl-ureido)-pyrrolidin-1-yl]-purin-9-yl}-2,3-dihydroxy-cyclopentyl)-2-hydroxy-propionamide

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (R)—N-((1S,2R,3S,4R)-4-{6-(2,2-diphenyl-ethylamino)-2-[(R)-3-(3-pyridin-3-yl-ureido)-pyrrolidin-1-yl]-purin-9-yl}-2,3-dihydroxy-cyclopentyl)-2-phenoxy-propionamide (83 mg, 0.104 mmol) in EtOH (20 ml) and THF (5 ml) under an inert atmosphere is treated with palladium hydroxide (20% w/w on carbon, 32 mg) followed by acetic acid (2 ml). The reaction mixture is placed under an atmosphere of hydrogen for two weeks after which time, the mixture is filtered and concentrated in vacuo. The resulting crude product is washed with EtOH (3 times), filtered and then concentrated in vacuo. The residue is dissolved in MeOH (2 ml) and purification by reverse phase column chromatography (Isolute™ C18, 0-100% acetonitrile in water—0.1% NH3) affords the title compound as a white solid. (MH+ 707.4)

Workup

  1. waitThe reaction mixture is placed under an atmosphere of hydrogen for two weeks
  2. filtrationafter which time, the mixture is filtered
  3. concentrationconcentrated in vacuo
  4. washThe resulting crude product is washed with EtOH (3 times)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue is dissolved in MeOH (2 ml)
  8. custompurification by reverse phase column chromatography (Isolute™ C18, 0-100% acetonitrile in water—0.1% NH3)

Sources & evidence

ORD record
ord-12174f44f0514e59829e9b3e4b906e84
Source dataset
uspto-grants-2012_09
Patent number
US08258141B2

Reaction notes

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