Tetrahydrofuran → 6-{[2,2-Bis(3-methyl phenyl)ethyl]amino}-N-[2-[({[2-(diisopropylamino)ethyl]amino}carbonyl)-amino]ethyl]-9-{(2R,3R,4S,5S)-5-[(ethylamino)carbonyl]-3,4-dihydroxytetrahydro-2-furanyl}-9H-purine-2-carboxamide

HRID 10431Notes

Reaction equation

HRID 10431 reaction equation
C([O:9][C@@H:10]1[C@H:14]([O:15]C(=O)C2C=CC=CC=2)[C@@H:13]([C:24]([NH:26][CH2:27][CH3:28])=[O:25])[O:12][C@H:11]1[N:29]1[CH:37]=[N:36][C:35]2[C:30]1=[N:31][C:32](I)=[N:33][C:34]=2[NH:38][CH2:39][CH:40]([C:48]1[CH:53]=[CH:52][CH:51]=[C:50]([CH3:54])[CH:49]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[C:43]([CH3:47])[CH:42]=1)(=O)C1C=CC=CC=1.[NH2:56][CH2:57][CH2:58][NH:59][C:60]([NH:62][CH2:63][CH2:64][N:65]([CH:69]([CH3:71])[CH3:70])[CH:66]([CH3:68])[CH3:67])=[O:61].C1C[O:75][CH2:74]C1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:54][C:50]1[CH:49]=[C:48]([CH:40]([C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([CH3:47])[CH:42]=2)[CH2:39][NH:38][C:34]2[N:33]=[C:32]([C:74]([NH:56][CH2:57][CH2:58][NH:59][C:60]([NH:62][CH2:63][CH2:64][N:65]([CH:69]([CH3:71])[CH3:70])[CH:66]([CH3:67])[CH3:68])=[O:61])=[O:75])[N:31]=[C:30]3[C:35]=2[N:36]=[CH:37][N:29]3[C@H:11]2[C@H:10]([OH:9])[C@H:14]([OH:15])[C@@H:13]([C:24]([NH:26][CH2:27][CH3:28])=[O:25])[O:12]2)[CH:53]=[CH:52][CH:51]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 21040857(2R,3R,4S,5S)-4-(benzoyloxy)-2-(6-{[2,2-bis(3-methylphenyl)ethyl]amino}-2-iodo-9H-purin-9-yl)-5-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoateHCID 21978253N-(2-aminoethyl)-N'-[2-(diisopropylamino)ethyl]urea

Product 1

HCID 600916706-{[2,2-Bis(3-methyl phenyl)ethyl]amino}-N-[2-[({[2-(diisopropylamino)ethyl]amino}carbonyl)-amino]ethyl]-9-{(2R,3R,4S,5S)-5-[(ethylamino)carbonyl]-3,4-dihydroxytetrahydro-2-furanyl}-9H-purine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A solution of (2R,3R,4S,5S)-4-(benzoyloxy)-2-(6-{[2,2-bis(3-methylphenyl)ethyl]amino}-2-iodo-9H-purin-9-yl)-5-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate (Preparation 48) (200 mg, 0.24 mmol), N-(2-aminoethyl)-N′-[2-(diisopropylamino)ethyl]urea (Preparation 52) (270 mg, 1.18 mmol) and tetrakis(triphenylphosphine)palladium(0) (27 mg, 0.024 mmol) in THF (5 ml) was carbonylated at 60° C. and 345 KPa under a carbon monoxide atmosphere for 14 hours. TLC analysis showed the desired product together with partially deprotected material. To achieve complete removal of the benzoate protecting groups, solvent was evaporated under reduced pressure, the residue dissolved in methanol (10 ml), sodium carbonate (10 mg) added and the mixture allowed to stir at room temperature for 24 hours. Solvent was again evaporated under reduced pressure and the residue purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol (90:10, by volume) changing to dichloromethane:methanol:concentrated aqueous ammonia (90:10:1, by volume). After evaporation of appropriate fractions the residue was triturated with diethyl ether, filtered and dried to yield the target compound as a white solid, (0.11 g, 61%).

Workup

  1. customwas carbonylated at 60° C.

Sources & evidence

ORD record
ord-7fde1ea0769641d099aecaf4a6f8b926
Source dataset
uspto-grants-2006_08
Patent number
US07094769B2

Reaction notes

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