Nitrogen → HCID 86671717, compound

HRID 330734Notes

Reaction equation

HRID 330734 reaction equation
N#N.[C:3]([CH2:5][CH2:6][O:7][P:8](Cl)[N:9]([CH:13]([CH3:15])[CH3:14])[CH:10]([CH3:12])[CH3:11])#[N:4].[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([C:64]2[CH:69]=[CH:68][C:67]([O:70][CH3:71])=[CH:66][CH:65]=2)([C:58]2[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=2)[O:26][CH2:27][C@H:28]2[O:32][C@@H:31]([N:33]3[CH:41]=[N:40][C:39]4[C:34]3=[N:35][CH:36]=[N:37][C:38]=4[O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[C@@H:30]([O:49][CH2:50][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)[C@@H:29]2[OH:57])=[CH:21][CH:20]=1.C(N(CC)C(C)C)(C)C.CN1C=CN=C1>CCOC(C)=O.CCCCCC.C(N(CC)CC)C.O1CCCC1>[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([C:64]2[CH:65]=[CH:66][C:67]([O:70][CH3:71])=[CH:68][CH:69]=2)([C:58]2[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=2)[O:26][CH2:27][C@H:28]2[O:32][C@@H:31]([N:33]3[CH:41]=[N:40][C:39]4[C:34]3=[N:35][CH:36]=[N:37][C:38]=4[O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[C@@H:30]([O:49][CH2:50][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)[C@@H:29]2[O:57][P:8]([O:7][CH2:6][CH2:5][C:3]#[N:4])[N:9]([CH:10]([CH3:11])[CH3:12])[CH:13]([CH3:14])[CH3:15])=[CH:21][CH:20]=1

Participants

10

Reactant 5

HCID 947NitrogenHCID 13901-MethylimidazoleHCID 81531DiisopropylethylamineHCID 27348442-Cyanoethyl N,N-diisopropylchlorophosphoramiditeHCID 68379366HCID 68379366, compound

Product 1

HCID 86671717HCID 86671717, compoundYield 94.8%

Reagents, catalysts & solvents 4

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Under the protection of N2, 2-cyanoethyl-N,N-diisopropylchlorophosphoramidite (0.69 mL, 3.10 mmol) was added drop-wise to a 0° C. anhydrous tetrahydrofuran (12 mL) solution of 9-{5-O-[bis(4-methoxyphenyl)(phenyl)methyl]-2-O-benzyl-β-D-arabinofuranosyl}-6-[2-(trimethylsilyl)ethoxy]-9H-purine (1.18 g g, 1.55 mmol), N,N-diisopropylethylamine (0.81 mL, 4.65 mmol)), and 1-methylimidazole (0.06 mL, 0.78 mmol). The reaction was gradually warmed to room temperature and stirred for 60 min. The reaction was then quenched with methanol (5 mL) and stirred for 5 min. After the solvent was removed under the reduced pressure, the residue was purified by flash chromatography (gradient: hexane with EtOAc 0-50%, with 1% triethylamine in both hexane and EtOAc) to produce 1.41 g (94.6%, 1.47 mmol) final product. LCMS: for C52H65N6O5PSi calculated 961.167. found 961.6 [M+H]+. 31P NMR (600 MHz, CD3CN) δ: 150.65, 150.24.

Workup

  1. customThe reaction was then quenched with methanol (5 mL)
  2. stirringstirred for 5 min
  3. customAfter the solvent was removed under the reduced pressure
  4. customthe residue was purified by flash chromatography (gradient

Sources & evidence

ORD record
ord-516c5b73918149c99f6408469c41d964
Source dataset
uspto-grants-2014_11
Patent number
US08877439B2

Reaction notes

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