N-{(1S,2R,3S,4R)-4-[2-((R)-3-amino-pyrrolidin-1-yl)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-propionamide → N-[(1S,2R,3S,4R)-4-[2-[(R)-3-(4,5-Dihydro-1H-imidazol-2-ylamino)-pyrrolidin-1-yl]-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl]-propionamide

HRID 1882575Notes

Reaction equation

HRID 1882575 reaction equation
[NH2:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[N:15]=[C:14]3[C:10]([N:11]=[CH:12][N:13]3[C@@H:16]3[CH2:20][C@H:19]([NH:21][C:22](=[O:25])[CH2:23][CH3:24])[C@@H:18]([OH:26])[C@H:17]3[OH:27])=[C:9]([NH:28][CH2:29][CH:30]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[N:8]=2)[CH2:3]1.I.[NH:44]1[CH2:48][CH2:47][N:46]=[C:45]1S>C(O)C.CN(C1C=CN=CC=1)C>[NH:46]1[CH2:47][CH2:48][N:44]=[C:45]1[NH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[N:15]=[C:14]3[C:10]([N:11]=[CH:12][N:13]3[C@@H:16]3[CH2:20][C@H:19]([NH:21][C:22](=[O:25])[CH2:23][CH3:24])[C@@H:18]([OH:26])[C@H:17]3[OH:27])=[C:9]([NH:28][CH2:29][CH:30]([C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=3)[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[N:8]=2)[CH2:3]1

Participants

5

Reactant 2

HCID 59781437N-{(1S,2R,3S,4R)-4-[2-((R)-3-amino-pyrrolidin-1-yl)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-propionamideHCID 178506615HCID 178506615, compound

Product 1

HCID 24863901N-[(1S,2R,3S,4R)-4-[2-[(R)-3-(4,5-Dihydro-1H-imidazol-2-ylamino)-pyrrolidin-1-yl]-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl]-propionamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 702EthanolSolvent

Procedure

A mixture comprising N-{(1S,2R,3S,4R)-4-[2-((R)-3-amino-pyrrolidin-1-yl)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-propionamide (Example 18 step 2) (30 mg, 0.053 mmol) and 4,5-dihydro-1H-imidazole-2-thiol hydroiodide (24 mg, 0.106 mmol) in absolute ethanol (2 ml) is treated with DMAP (catalytic amount) and TEA (29 μl, 0.212 mmol). The resulting mixture is heated using microwave radiation in a Personal Chemistry Emrys™ Optimizer microwave reactor at 150° C. for 4000 s. The solvent is removed in vacuo and purification of the crude product by preparative HPLC ((30-95% acetonitrile in water −0.1% TFA) affords the title compound. (MH+ 639.63)

Workup

  1. temperatureThe resulting mixture is heated
  2. customat 150° C.
  3. customfor 4000 s
  4. customThe solvent is removed in vacuo and purification of the crude product by preparative HPLC ((30-95% acetonitrile in water −0.1% TFA)

Sources & evidence

ORD record
ord-c2f94d61dd014a899e5cdd20b2a4471b
Source dataset
uspto-grants-2012_11
Patent number
US08318750B2

Reaction notes

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