2-Cyanoethyl tetraisopropylphosphorodiamidite → HCID 90411800, compound

HRID 1754601Notes

Reaction equation

HRID 1754601 reaction equation
[C:1]([NH:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[CH2:19][C@@H:20]([C@H:46]([OH:48])[CH3:47])[CH2:21][O:22][C:23]([C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][CH:39]=1)([C:30]1[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1[C-]=NN=N1.C([NH2+]C(C)C)(C)C.[CH:61]([N:64]([CH:78]([CH3:80])[CH3:79])[P:65](N(C(C)C)C(C)C)[O:66][CH2:67][CH2:68][C:69]#[N:70])([CH3:63])[CH3:62]>ClCCl>[CH:78]([N:64]([CH:61]([CH3:63])[CH3:62])[P:65]([O:66][CH2:67][CH2:68][C:69]#[N:70])[O:48][C@H:46]([CH3:47])[C@H:20]([CH2:19][N:14]1[CH:13]=[N:12][C:11]2[C:15]1=[N:16][CH:17]=[N:18][C:10]=2[NH:9][C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:21][O:22][C:23]([C:38]1[CH:39]=[CH:40][C:41]([O:44][CH3:45])=[CH:42][CH:43]=1)([C:30]1[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([CH3:80])[CH3:79]

Participants

5

Reactant 3

HCID 1281532-Cyanoethyl tetraisopropylphosphorodiamidite2×HCID 90412648HCID 90412648, compoundHCID 178458033HCID 178458033, compound

Product 1

HCID 90411800HCID 90411800, compoundYield 93.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 14 (0.9 g, 1.4 mmol) in 20 ml of anhydrous dichloromethane was added diisopropylammonium tetrazolide (0.25 g) followed by 0.5 g (1.66 mmol) of 2-cyanoethyl N,N,N′,N′-tetraisopropylphosphordiamidite. In about 5 hrs another 0.04 g of 2-cyanoethyl N,N,N′,N′-tetraisopropylphosphordiamidite was added. The reaction was allowed to proceed for total 20 hrs and then concentrated. The resultant semi-solid was 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 (˜5-10 ml) amount of ethyl acetate, diluting with hexane (100 ml), allowing to settle as an oil and decanting the liquid. Drying in vacuo afforded 1.1 g (93%) of 15 as a white amorphous solid. 31P NMR (DMSO-d6): δ 147.11, 146.16.

Workup

  1. concentrationconcentrated
  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 (˜5-10 ml) amount of ethyl acetate
  7. additiondiluting with hexane (100 ml)
  8. customdecanting the liquid
  9. customDrying in vacuo

Sources & evidence

ORD record
ord-076d99acd19a4ff4b157bb62182b6620
Source dataset
uspto-grants-2015_10
Patent number
US09169256B2

Reaction notes

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