(R)-3-N-Cbz-aminopyrrolidine → {(R)-1-[9-((1R,2S,3R,4S)-2,3-dihydroxy-4-propionylamino-cyclopentyl)-6-(2,2-diphenyl-ethylamino)-9H-purin-2-yl]-pyrrolidin-3-yl}-carbamic acid benzyl ester

HRID 1696974Notes

Reaction equation

HRID 1696974 reaction equation
[CH2:1]([O:8][C:9](=[O:16])[NH:10][C@@H:11]1[CH2:15][CH2:14][NH:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:18]1[N:26]=[C:25]2[C:21]([N:22]=[CH:23][N:24]2[C@@H:27]2[CH2:31][C@H:30]([NH:32][C:33](=[O:36])[CH2:34][CH3:35])[C@@H:29]([OH:37])[C@H:28]2[OH:38])=[C:20]([NH:39][CH2:40][CH:41]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[N:19]=1>CN1C(=O)CCC1>[CH2:1]([O:8][C:9](=[O:16])[NH:10][C@@H:11]1[CH2:15][CH2:14][N:13]([C:18]2[N:26]=[C:25]3[C:21]([N:22]=[CH:23][N:24]3[C@@H:27]3[CH2:31][C@H:30]([NH:32][C:33](=[O:36])[CH2:34][CH3:35])[C@@H:29]([OH:37])[C@H:28]3[OH:38])=[C:20]([NH:39][CH2:40][CH:41]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[C:48]3[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=3)[N:19]=2)[CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 40425229(R)-3-N-Cbz-aminopyrrolidineHCID 86622630N-[(1S,2R,3S,4R)-4-[2-Chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl]-propionamide

Product 1

HCID 24863132{(R)-1-[9-((1R,2S,3R,4S)-2,3-dihydroxy-4-propionylamino-cyclopentyl)-6-(2,2-diphenyl-ethylamino)-9H-purin-2-yl]-pyrrolidin-3-yl}-carbamic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of (R)-pyrrolidin-3-yl-carbamic acid benzyl ester hydrochloride (0.88 g, 3.45 mmol) in DCM is free-based using sodium hydrogen carbonate solution to yield (R)-pyrrolidin-3-yl-carbamic acid benzyl ester (0.487 g, 2.22 mmol). This amine is added to N-{(1S,2R,3S,4R)-4-[2-chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-propionamide (Example 4) (0.5 g, 0.96 mmol) and TEA (0.224 g, 2.22 mmol) and then dissolved in NMP (7 ml). The reaction mixture is heated using microwave radiation in a Personal Chemistry Emrys™ Optimizer microwave reactor at 190° C. for 1 hour. The resulting mixture is purified by chromatography on silica eluting with 5% MeOH in DCM to yield the titled compound.

Workup

  1. temperatureThe reaction mixture is heated
  2. customat 190° C.
  3. customfor 1 hour
  4. customThe resulting mixture is purified by chromatography on silica eluting with 5% MeOH in DCM

Sources & evidence

ORD record
ord-02afe82161244b76a881e73b30db958a
Source dataset
uspto-grants-2012_04
Patent number
US08163754B2

Reaction notes

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