Lithium Hexamethyldisilazide → HCID 59548358, compound

HRID 1621664Notes

Reaction equation

HRID 1621664 reaction equation
Cl[C:2]1[C:7]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([NH2:15])[N:9]=2)=[CH:6][C:5]([F:16])=[CH:4][N:3]=1.[F:17][C:18]1[CH:19]=[C:20]([NH2:26])[CH:21]=[N:22][C:23]=1[O:24][CH3:25].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[F:16][C:5]1[CH:6]=[C:7]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([NH2:15])[N:9]=2)[C:2]([NH:26][C:20]2[CH:21]=[N:22][C:23]([O:24][CH3:25])=[C:18]([F:17])[CH:19]=2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 454803515-Fluoro-6-methoxypyridin-3-amineHCID 86647057HCID 86647057, compound

Product 1

HCID 59548358HCID 59548358, compoundYield 41.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-(2-chloro-5-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (100 mg, 0.417 mmol) and 5-fluoro-6-methoxypyridin-3-amine (120 mg, 0.844 mmol) (Anichem, N.J., USA) in THF (2.0 mL) was cooled in an ice bath under nitrogen. A THF solution of LiHMDS (1 M in THF, 2500 μL, 2.500 mmol) was added dropwise. After 5 min, the cooling bath was removed. After a total of 22 min, HCl (5N, 0.5 mL) was added. After 5 min, EtOAc (10 mL) and saturated NH4Cl (10 mL) were added. The organic layer was washed with water (2×5 mL). The combined aqueous layers were extracted with EtOAc (2×5 mL). The combined organic layers were dried over Na2SO4 and concentrated. The resulting residue was suspended in MeOH (5 mL) and filtered. The solid was washed with MeOH (2×2 mL), DCM (3×3 mL) and EtOAc (3×3 mL) to give the first batch of product as a brown solid. The combined washings were concentrated and purified on silica using 0-3% MeOH in DCM. The dark blue fraction contained the desired product (m/z 346) as a second batch. The combined product batches was suspended in ether (4 mL) and filtered to give the final product as a green solid (60 mg). LCMS (ES, pos.): calcd for C15H13F2N7O: 345.1. found: 346.2 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 11.78 (s, 1H); 8.56 (dd, J=9.78, 2.93 Hz, 1H); 8.38 (br. s., 2H); 8.28 (dd, J=12.81, 1.86 Hz, 1H); 7.97 (br. s., 1H); 7.84 (br. s., 1H); 3.93 (s, 3H); 2.44 (s, 3H). 19F NMR (377 MHz, d6-DMSO) δ −140.84 (s, 1F); −139.70 (s, 1F).

Workup

  1. customthe cooling bath was removed
  2. additionAfter a total of 22 min, HCl (5N, 0.5 mL) was added
  3. waitAfter 5 min
  4. additionEtOAc (10 mL) and saturated NH4Cl (10 mL) were added
  5. washThe organic layer was washed with water (2×5 mL)
  6. extractionThe combined aqueous layers were extracted with EtOAc (2×5 mL)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. concentrationconcentrated
  9. filtrationfiltered
  10. washThe solid was washed with MeOH (2×2 mL), DCM (3×3 mL) and EtOAc (3×3 mL)
  11. customto give the first batch of product as a brown solid
  12. concentrationThe combined washings were concentrated
  13. custompurified on silica using 0-3% MeOH in DCM
  14. filtrationfiltered

Sources & evidence

ORD record
ord-4ea31733e3524d2b861e139a6a2125fb
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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