Triethylamine → HCID 178491468, compound

HRID 889780Notes

Reaction equation

HRID 889780 reaction equation
[C:1]([CH2:3][CH2:4][PH:5]([O:14][C@@H:15]1[C@@H:19]([CH2:20][O:21][C:22]([C:37]2[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=2)([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[O:18][C@@H:17](N2C=CC(=O)NC2=O)[C@@H:16]1[O:53][C:54](=[O:62])[NH:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)([N:7]([CH:11]([CH3:13])[CH3:12])[CH:8]([CH3:10])[CH3:9])[OH:6])#[N:2].[O:63]=P(Cl)(Cl)Cl.C(N([CH2:73][CH3:74])CC)C.[NH:75]1[CH:79]=[N:78][CH:77]=[N:76]1>N1C=CC=CC=1.N.C(OCC)(=O)C.C(#N)C>[C:1]([CH2:3][CH2:4][PH:5]([O:14][C@@H:15]1[C@@H:19]([CH2:20][O:21][C:22]([C:29]2[CH:30]=[CH:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=2)([C:37]2[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[O:18][C@@H:17]([N:76]2[CH:74]=[CH:73][C:79]([NH2:75])=[N:78][C:77]2=[O:63])[C@@H:16]1[O:53][C:54](=[O:62])[NH:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)([N:7]([CH:11]([CH3:13])[CH3:12])[CH:8]([CH3:9])[CH3:10])[OH:6])#[N:2]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 92571H-1,2,4-TriazoleHCID 24813Phosphorus oxychlorideHCID 178491470HCID 178491470, compound

Product 1

HCID 178491468HCID 178491468, compoundYield 93%

Reagents, catalysts & solvents 4

HCID 222AmmoniaSolventHCID 1049PyridineSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the acetonitrile solution of 5′-O-[bis(4-methoxyphenyl)phenylmethyl]-2′-O-phenylcarbamoyl-uridine 3′-O-(2-cyanoethyl N,N-diisopropylphosphoramidite) (0.88 mmol, 765.5 mg) and POCl3 (1.88 mmol, 287.5 mg) and triethylamine (21.6 mmol, 2.186 g), 1,2,4-triazole (20.7 mmol, 1.459 g) was added dropwise at room temperature. The mixture was stirred for 2 hours. Ethyl acetate (150 ml) was added thereto, and the organic layer was washed with a 5% Na2CO3 aqueous solution twice and distilled water once. The organic layer was dried with anhydrous sodium sulfate, and concentrated to obtain a pale yellow solid. The solid was dissolved in a mixed solvent of pyridine and ammonia, and the solution was stirred for 2.8 hours at room temperature. The solvent was distilled away, and the residue was subject to azeotropy with toluene and purified with silica gel column chromatography. The isolated yield was 93%.

Workup

  1. washthe organic layer was washed with a 5% Na2CO3 aqueous solution twice
  2. distillationdistilled water once
  3. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customto obtain a pale yellow solid
  6. stirringthe solution was stirred for 2.8 hours at room temperature
  7. distillationThe solvent was distilled away
  8. custompurified with silica gel column chromatography

Sources & evidence

ORD record
ord-38b890772c2f47d5bd6df769d8bdb8a2
Source dataset
uspto-grants-2012_08
Patent number
US08252919B2

Reaction notes

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