2,4-Dichloropyrimidine → HCID 178463181, compound

HRID 1014958Notes

Reaction equation

HRID 1014958 reaction equation
[C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([C:14]2[N:15]=[N:16][N:17]([CH2:19][CH3:20])[N:18]=2)[O:7][C@H:6]1[N:21]1[CH:29]=[N:28][C:27]2[C:22]1=[N:23][C:24]([Cl:45])=[N:25][C:26]=2[NH:30][C@H:31]1[CH2:36][CH2:35][C@H:34]([NH:37]C(OC(C)(C)C)=O)[CH2:33][CH2:32]1)(=[O:3])[CH3:2].FC(F)(F)C(O)=O.ClCCl.C(N(CC)C(C)C)(C)C.[Cl:65][C:66]1[N:71]=[C:70](Cl)[CH:69]=[CH:68][N:67]=1>CC(O)C>[C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([C:14]2[N:15]=[N:16][N:17]([CH2:19][CH3:20])[N:18]=2)[O:7][C@H:6]1[N:21]1[CH:29]=[N:28][C:27]2[C:22]1=[N:23][C:24]([Cl:45])=[N:25][C:26]=2[NH:30][C@H:31]1[CH2:32][CH2:33][C@H:34]([NH:37][C:70]2[CH:69]=[CH:68][N:67]=[C:66]([Cl:65])[N:71]=2)[CH2:35][CH2:36]1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 775312,4-DichloropyrimidineHCID 81531DiisopropylethylamineHCID 21863450Trifluoroacetic acid methylene chlorideHCID 178463187HCID 178463187, compound2×

Product 1

HCID 178463181HCID 178463181, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
60 °C

Procedure

(2R,3R,4R,5R)-2-(2-Chloro-6-{[trans-4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)cyclohexyl]amino}-9H-purin-9-yl)-5-(2-ethyl-2H-tetrazol-5-yl)tetrahydrofuran-3,4-diyl diacetate (Intermediate 1) (5.4 mmol) was treated with 1:1 trifluoroacetic acid/dichloromethane (20 ml) at room temperature for ca. 1 h. This was concentrated in vacuo and the residue was partitioned between dichloromethane (50 ml) and aqueous sodium bicarbonate (50 ml). The organics were washed with aqueous sodium bicarbonate (50 ml), dried over sodium sulfate and concentrated in vacuo to give a white solid. This was dissolved in propan-2-ol (100 ml). To this was added N,N-diisopropylethylamine (4 m. eq.) and 2,4-dichloropyrimidine (1 m. eq.). The reaction mixture was heated at 60° C. overnight. The reaction mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate (50 ml) and water (50 ml). The organics were washed with water (50 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by SPE (50 g, silica) eluting with x% ethyl acetate in dichloromethane where x=25, 50, 75. Fractions containing desired product were combined and concentrated in vacuo to yield the title compound as a colourless gum, 1.49 g.

Workup

  1. concentrationThis was concentrated in vacuo
  2. customthe residue was partitioned between dichloromethane (50 ml) and aqueous sodium bicarbonate (50 ml)
  3. washThe organics were washed with aqueous sodium bicarbonate (50 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give a white solid
  7. concentrationThe reaction mixture was concentrated in vacuo
  8. customthe residue was partitioned between ethyl acetate (50 ml) and water (50 ml)
  9. washThe organics were washed with water (50 ml)
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated in vacuo
  12. customThe crude product was purified by SPE (50 g, silica)
  13. washeluting with x% ethyl acetate in dichloromethane where x=25, 50, 75
  14. additionFractions containing desired product
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f5eeb5322bd54178ac5d78db36a5cb1e
Source dataset
uspto-grants-2011_07
Patent number
US07985740B2

Reaction notes

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