Acetonitrile → HCID 178522337, compound

HRID 1055255Notes

Reaction equation

HRID 1055255 reaction equation
CC[N:3]([CH2:6][CH3:7])[CH2:4]C.S(Cl)(C1C=CC(C)=CC=1)(=O)=O.[NH4+:19].[OH-:20].[C:21](Cl)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:22].C[C:31]#[N:32]>CN(C1C=CN=CC=1)C.C(Cl)Cl.N1C=CC=CC=1.O>[C:21]([NH:19][C:31]1[CH:7]=[CH:6][NH:3][C:4](=[O:20])[N:32]=1)(=[O:22])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

10

Reactant 5

HCID 6342AcetonitrileHCID 73974-Toluenesulfonyl chlorideHCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 14923Ammonium Hydroxide

Product 1

HCID 178522337HCID 178522337, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of compound 43 (0.08 g, 0.14 mmol) in MeCN (10 mL) was added DMAP (0.02 g, 0.14 mmol) and Et3N (0.07 g, 0.71 mmol) followed by addition of TsCl (0.08 g, 0.43 mmol) and the solution was stirred at room temperature for 1 h. To the solution was added NH4OH (30%, 2 mL) and the mixture was stirred at room temperature for 1 h. Solvent was evaporated to dryness and the residue was co-evaporated with toluene twice to give crude cytosine analog which was dissolved in CH2Cl2 (10 mL) and pyridine (1 mL). To the solution was added BzCl (0.1 mL, 0.86 mmol) and the solution was stirred at room temperature for 2 h. Water (5 mL) was added and the mixture was evaporated to dryness under reduced pressure. The residue was dissolved in EtOAc (100 mL) and the solution was washed with water, brine and dried over Na2SO4. Solvent was evaporated and the residue was purified by silica gel column chromatography (0-60% EtOAc in hexanes) to give N-benzoylcytosine analog which was dissolved in THF (10 mL). To the solution was added TBAF (0.12 g, 0.48 mmol) and the solution was stirred at room temperature for 1 h. Solvent was evaporated and the residue was purified by silica gel column (0-8% MeOH in CH2Cl2) to give N-benzoyl nucleoside which was dissolved in 7N NH3 in MeOH (8 mL) and the solution was stirred at room temperature for 20 h. Solvent was evaporated and the residue was purified by silica gel column (0-30% MeOH in CH2Cl2) to give product 49 (0.09 g, 56% from 43). 1H NMR (400 MHz, CD3OD) δ: 8.09 (d, J=7.6 Hz, 1H), 5.99 (s, 1H), 5.87 (d, J=7.6 Hz, 1H), 3.95 (m, 6H), 2.80 (m, 4H). LC-MS (ESI): 284 [M+H]+.

Workup

  1. stirringthe mixture was stirred at room temperature for 1 h
  2. customSolvent was evaporated to dryness
  3. customto give crude cytosine analog which
  4. stirringthe solution was stirred at room temperature for 2 h
  5. customthe mixture was evaporated to dryness under reduced pressure
  6. dissolutionThe residue was dissolved in EtOAc (100 mL)
  7. washthe solution was washed with water, brine
  8. dry with materialdried over Na2SO4
  9. customSolvent was evaporated
  10. customthe residue was purified by silica gel column chromatography (0-60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-158233bdddf64f2681ff98f572ead2db
Source dataset
uspto-grants-2016_07
Patent number
US09394331B2

Reaction notes

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