HCID 66778977, compound → HCID 66779277, compound

HRID 408999Notes

Reaction equation

HRID 408999 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[C@:15]([CH3:17])([OH:16])[C@H:14]([OH:18])[C@@H:13]([CH2:19][OH:20])[O:12]2)=[C:4]([O:21][CH3:22])[N:3]=1.C([Mg]Cl)(C)(C)C.Cl[C:30]1[CH:39]=[CH:38][C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]=1[O:40][P:41](=[N:43][C@@H:44]([C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)[C:45]([O:47][CH:48]1[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]1)=[O:46])=[O:42]>C1COCC1>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[O:12][C@H:13]([CH2:19][O:20][C:30]3[CH:39]=[CH:38][C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[C:31]=3[O:40][P:41](=[N:43][C@@H:44]([C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=3)[C:45]([O:47][CH:48]3[CH2:49][CH2:50][CH2:51][CH2:52][CH2:53]3)=[O:46])=[O:42])[C@@H:14]([OH:18])[C@:15]2([OH:16])[CH3:17])=[C:4]([O:21][CH3:22])[N:3]=1

Participants

5

Reactant 3

HCID 66778977HCID 66778977, compoundHCID 66780049HCID 66780049, compoundHCID 178418310HCID 178418310, compound

Product 1

HCID 66779277HCID 66779277, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Using the general procedure (Method B) for the synthesis of nucleoside 5′-phosphoramidates to a solution of 250 mg of (3R,4R,5R)-2-(2-amino-6-methoxy-9H-purin-9-yl)-5-(hydroxymethyl)-3-methyltetrahydrofuran-3,4-diol in 5 mL of THF was added tert-BuMgCl (1.61 mL) followed by (2S)-cyclohexyl 2-(chloro(naphthalen-1-yloxy)phosphorylamino)-2-phenylacetate (1.10 g) in THF (5 mL). After workup and silica gel column chromatography, 310 mg of (2S)-cyclohexyl 2-((((2R,3R,4R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yloxy)phosphorylamino)-2-phenylacetate was obtained (53% yield). HPLC tR=21.47, 21.65 min (column: Varian Pursuit XRs 5, C18, 150×4.6 mm; method: linear gradient of ACN (10% to 100%) in H2O in 30 min).

Sources & evidence

ORD record
ord-e846b3478b7e42b9926a81b030401e26
Source dataset
uspto-grants-2014_06
Patent number
US08759318B2

Reaction notes

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