Sodium hydride → 7-Amino-1-[(1,3-dibenzoyloxy-2-propoxy)methyl]-1,3-azaphospholo[4,5-d]pyrimidine

HRID 1108784Notes

Reaction equation

HRID 1108784 reaction equation
[NH2:1][C:2]1[C:3]2[NH:10][CH:9]=[P:8][C:4]=2[N:5]=[CH:6][N:7]=1.[H-].[Na+].[C:13]([O:21][CH2:22][CH:23]([O:34][CH2:35]Br)[CH2:24][O:25][C:26](=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CN(C=O)C>[NH2:1][C:2]1[C:3]2[N:10]([CH2:35][O:34][CH:23]([CH2:22][O:21][C:13](=[O:20])[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:24][O:25][C:26](=[O:33])[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:9]=[P:8][C:4]=2[N:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 13964459(1,3-Dibenzoyloxy-2-propoxy)methyl bromideHCID 178508727HCID 178508727, compound2×

Product 1

HCID 187837337-Amino-1-[(1,3-dibenzoyloxy-2-propoxy)methyl]-1,3-azaphospholo[4,5-d]pyrimidineYield 44.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 7-amino-1H-1,3-azaphospholo[4,5-d]pyrimidine (compound 10, 0.5 g, 3.29 mmol) in DMF (20 mL) was added NaH (0.16 g, 4 mmol) under an argon atmosphere. After stirring the mixture at room temperature for 40 min, (1,3-dibenzoyloxy-2-propoxy)methyl bromide (109) (1.38 g, 3.5 mmol) was added and the reaction was continued for 18 h. The solvent was evaporated in vacuo. The residue was dissolved in dichloromethane (150 mL) and the organic solution was washed with water (30 mL). Aqueous layer was extracted with dichloromethane (2×100 mL) and the combined organic extracts were dried (Na2SO4) and evaporated. The residue was purified by silica gel column (2×15 cm) chromatography. The column was flash eluted with dichloromethane containing 0-2.5% methanol. The appropriate fractions containing the desired product were evaporated to yield 0.68 g (44%) of the title compound, mp 148-150° C. 1H nmr (DMSO-d6): δ 4.35 (m, 3 H, CH, CH2), 4.52 (m, 2 H, CH2), 5.79 (s, 2 H, CH2), 7.45-7.75 (m, 10 H, 2 Bz), 8.33 (s, 2 H, NH2), 8.66 (d, 1 H, C5H), and 8.81 (d, 1 H, J =57.9 Hz, C2H ). Anal. Calcd. for C23H21N4O5P: C, 59.48; H, 4.56; N, 12.07. Found: C, 59.08; H, 4.56; N, 12.02.

Workup

  1. waitthe reaction was continued for 18 h
  2. customThe solvent was evaporated in vacuo
  3. dissolutionThe residue was dissolved in dichloromethane (150 mL)
  4. washthe organic solution was washed with water (30 mL)
  5. extractionAqueous layer was extracted with dichloromethane (2×100 mL)
  6. dry with materialthe combined organic extracts were dried (Na2SO4)
  7. customevaporated
  8. customThe residue was purified by silica gel column (2×15 cm) chromatography
  9. washeluted with dichloromethane containing 0-2.5% methanol
  10. additionThe appropriate fractions containing the desired product
  11. customwere evaporated

Sources & evidence

ORD record
ord-4a978a19fb954b708b735fe6996779e1
Source dataset
uspto-grants-2000_05
Patent number
US06069132

Reaction notes

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