2-Cyanoethyl tetraisopropylphosphorodiamidite → (2R,3R)-1-(Bis(4-methoxyphenyl)(phenyl)methoxy)-2-((4-acetamido-2-oxo-pyrimidin-1(2H)-yl)methyl)butan-3-yl 2-cyanoethyl N,N-diisopropylphosphoramidite

HRID 1754607Notes

Reaction equation

HRID 1754607 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:10][CH2:11][C@@H:12]([CH2:16][N:17]2[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:26])[CH3:25])=[N:19][C:18]2=[O:27])[C@H:13]([OH:15])[CH3:14])=[CH:5][CH:4]=1.N1[C-]=NN=N1.C([NH2+]C(C)C)(C)C.[CH:54]([N:57]([CH:71]([CH3:73])[CH3:72])[P:58](N(C(C)C)C(C)C)[O:59][CH2:60][CH2:61][C:62]#[N:63])([CH3:56])[CH3:55]>ClCCl>[CH:71]([N:57]([CH:54]([CH3:56])[CH3:55])[P:58]([O:59][CH2:60][CH2:61][C:62]#[N:63])[O:15][C@H:13]([CH3:14])[C@H:12]([CH2:16][N:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:26])[CH3:25])=[N:19][C:18]1=[O:27])[CH2:11][O:10][C:9]([C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=1)([C:34]1[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([CH3:73])[CH3:72]

Participants

5

Reactant 3

HCID 1281532-Cyanoethyl tetraisopropylphosphorodiamiditeHCID 90413107(2R,3R)-1-(Bis(4-methoxyphenyl)(phenyl)methoxy)-2-((4-acetamido-2-oxo-pyrimidin-1(2H)-yl)methyl)butan-3-olHCID 178458033HCID 178458033, compound

Product 1

HCID 90411606(2R,3R)-1-(Bis(4-methoxyphenyl)(phenyl)methoxy)-2-((4-acetamido-2-oxo-pyrimidin-1(2H)-yl)methyl)butan-3-yl 2-cyanoethyl N,N-diisopropylphosphoramiditeYield 88.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 22 (1.0 g, 1.79 mmol) in 25 ml of anhydrous dichloromethane was added diisopropylammonium tetrazolide (0.35 g) followed by 0.8 g (2.66 mmol) of 2-cyanoethyl N,N,N′,N′-tetraisopropylphosphordiamidite. After being stirred at room temperature for 20 hrs the reaction was concentrated, and the residue portioned between ethyl acetate and saturated NaHCO3. The organic phase was washed with saturated NaCl, dried over Na2SO4 and concentrated in vacuo. The crude phosphoramidite was precipitated twice by re-dissolving in small (˜10 ml) amount of ethyl acetate, diluting with hexane (100 ml), allowing precipitate as an oil and decanting the liquid. Drying in vacuo afforded 1.2 g (88%) of 23 as an amorphous white solid. 31P NMR (DMSO-d6): δ 148.03, 147.19.

Workup

  1. concentrationwas concentrated
  2. washThe organic phase was washed with saturated NaCl
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude phosphoramidite was precipitated twice
  6. dissolutionby re-dissolving in small (˜10 ml) amount of ethyl acetate
  7. additiondiluting with hexane (100 ml)
  8. customdecanting the liquid
  9. customDrying in vacuo

Sources & evidence

ORD record
ord-439c102f800c4113817f1eda10a2ed5a
Source dataset
uspto-grants-2015_10
Patent number
US09169256B2

Reaction notes

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