Nitrogen → HCID 178491475, compound

HRID 330732Notes

Reaction equation

HRID 330732 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].[CH2:17]([O:24][C@@H:25]1[C@H:29]([OH:30])[C@@H:28]([CH2:31][O:32][C:33]([C:48]2[CH:53]=[CH:52][C:51]([O:54][CH3:55])=[CH:50][CH:49]=2)([C:40]2[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=2)[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:27][C@H:26]1[N:56]1[C:65]2[N:64]=[CH:63][N:62]=[C:60]([OH:61])[C:59]=2[N:58]=[CH:57]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(N(CC)C(C)C)(C)C.CN1C=CN=C1>CO.C(Cl)Cl.C(N(CC)CC)C.O1CCCC1>[CH2:17]([O:24][C@@H:25]1[C@H:29]([O:30][P:8]([O:7][CH2:6][CH2:5][C:3]#[N:4])[N:9]([CH:13]([CH3:15])[CH3:14])[CH:10]([CH3:12])[CH3:11])[C@@H:28]([CH2:31][O:32][C:33]([C:48]2[CH:53]=[CH:52][C:51]([O:54][CH3:55])=[CH:50][CH:49]=2)([C:40]2[CH:41]=[CH:42][C:43]([O:46][CH3:47])=[CH:44][CH:45]=2)[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:27][C@H:26]1[N:56]1[C:65]2[N:64]=[CH:63][N:62]=[C:60]([OH:61])[C:59]=2[N:58]=[CH:57]1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

10

Reactant 5

HCID 947NitrogenHCID 13901-MethylimidazoleHCID 81531DiisopropylethylamineHCID 27348442-Cyanoethyl N,N-diisopropylchlorophosphoramiditeHCID 178491474HCID 178491474, compound

Product 1

HCID 178491475HCID 178491475, compoundYield 78.3%

Reagents, catalysts & solvents 4

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

Under the protection of N2, 2-cyanoethyl-N,N-diisopropylchlorophosphoramidite (1.21 mL, 5.45 mmol) was added drop-wise to a 0° C. anhydrous tetrahydrofuran (12 mL) solution of 2′-O-benzyl-5′-O-[bis(4-methoxyphenyl)(phenyl)methyl]inosine (1.80 g, 2.72 mmol), N,N-diisopropylethylamine (1.42 mL, 8.17 mmol)), and 1-methylimidazole (0.11 mL, 1.36 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: methylene chloride with methanol 0-4%, with 1% triethylamine in both methylene chloride and methanol) to produce 1.83 g (78%, 2.13 mmol) final product. LCMS: for C47H53N6O8P calculated 860.4. found 861.3 [M+H]+ and 884.4 [M+Na]+. 31P NMR (600 MHz, CD3CN) δ: 150.82, 150.55.

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-d9960de7568f47e89c14abe45cd24c1f
Source dataset
uspto-grants-2014_11
Patent number
US08877439B2

Reaction notes

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