Lithium Hexamethyldisilazide → HCID 118036625, compound

HRID 1777853Notes

Reaction equation

HRID 1777853 reaction equation
[CH3:1][O:2][CH:3]([O:23][CH3:24])[C:4]1[N:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][N:11]2[C:14]([O:16]C2C=CC=CC=2)=O)=[CH:6][CH:5]=1.[NH2:25][C:26]1[N:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][N:27]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[C:32]([C:29]1[CH:28]=[N:27][C:26]([NH:25][C:14]([N:11]2[C:12]3[C:7](=[CH:6][CH:5]=[C:4]([CH:3]([O:2][CH3:1])[O:23][CH3:24])[N:13]=3)[CH2:8][CH2:9][CH2:10]2)=[O:16])=[N:31][CH:30]=1)#[N:33]

Participants

5

Reactant 3

HCID 2733832Lithium Hexamethyldisilazide2×HCID 38144922-Aminopyrimidine-5-carbonitrile2×HCID 118037161phenyl 7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate2×

Product 1

HCID 118036625HCID 118036625, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of phenyl 7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (intermediate 3, 50 mg, 0.152 mmol) in THF (1.5 ml) was treated with 2-amino-5-cyanopyrimidine (45.7 mg, 0.381 mmol), cooled to 0° C. and treated with LHMDS (1M in THF, 0.305 ml, 0.305 mmol). The reaction mixture was stirred at 0° C. for 1 h, allowed to warm to room temperature and stirred for 45 min. More 2-amino-5-cyanopyrimidine (22.9 mg, 0.190 mmol) and LHMDS (1M in THF, 0.152 ml, 0.152 mmol) were added, the reaction mixture was stirred for 35 min, quenched by addition of sat. aq. NH4Cl and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100). The product containing fractions were concentrated and re-purified by reverse phase chromatography (13 g C18 cartridge, 0.1% TFA in water/acetonitrile 95:5 to 5:95). The product containing fractions were treated with sat. aq. NaHCO3, concentrated until the organic solvent had been removed and extracted with DCM (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give the title compound as a white solid. (UPLC-MS 1) tR 0.87 min; ESI-MS 355.2 [M+H]+.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 45 min
  3. stirringthe reaction mixture was stirred for 35 min
  4. customquenched by addition of sat. aq. NH4Cl
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100)
  11. additionThe product containing fractions
  12. concentrationwere concentrated
  13. customre-purified by reverse phase chromatography (13 g C18 cartridge, 0.1% TFA in water/acetonitrile 95:5 to 5:95)
  14. additionThe product containing fractions
  15. additionwere treated with sat. aq. NaHCO3
  16. concentrationconcentrated until the organic solvent
  17. customhad been removed
  18. extractionextracted with DCM (3×)
  19. dry with materialThe combined organic layers were dried over Na2SO4
  20. filtrationfiltered
  21. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f373636af52641c89b5f4b6b10acc029
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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