5-Fluoro-3-pyridinamine → HCID 59548269, compound

HRID 1621665Notes

Reaction equation

HRID 1621665 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.[NH2:17][C:18]1[CH:19]=[N:20][CH:21]=[C:22]([F:24])[CH:23]=1.[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:17][C:18]2[CH:19]=[N:20][CH:21]=[C:22]([F:24])[CH:23]=2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 5744505-Fluoro-3-pyridinamineHCID 2733832Lithium HexamethyldisilazideHCID 86647057HCID 86647057, compound

Product 1

HCID 59548269HCID 59548269, compoundYield 16.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-(2-chloro-5-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (85 mg, 0.355 mmol) and 3-amino-5-fluoropyridine (118 mg, 1.053 mmol) in THF (3 mL) was cooled in an ice bath under nitrogen. After 5 min, a solution of LiHMDS (1 M in THF, 2500 μL, 2.500 mmol) was added. After 10 min, the cooling bath was removed. After 2 h, HCl (5 N, 0.5 mL) was added. EtOAc (10 mL) and saturated NH4Cl (10 mL) were added. The mixture was vigorously stirred for 15 min. The resulting emulsion was filtered through a glass frit. The collected solid was dissolved in warm DMSO and purified by prep HPLC (30-75% MeCN/water/w 0.1% TFA over 20 min). The collected product fractions were concentrated to dryness. Saturated NaHCO3 (10 mL) was added. The mixture was neutralized with HCl (5N) and filtered. The filtrate was extracted with iPrOH (5%) in CHCl3 (3×5 mL). The combined organic layers were dried over Na2SO4 and concentrated to a yellow solid which was filtered as a suspension in ether to give the product as a yellow powder (18 mg). LCMS (ES, pos.): calcd for C14H11F2N7: 315.1. found: 316.1 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.18 (s, 1H); 8.82 (s, 1H); 8.62 (dd, J=9.78, 3.13 Hz, 1H); 8.44-8.53 (m, 2H); 8.18 (d, J=2.54 Hz, 1H); 8.04 (br. s., 1H); 7.90 (br. s., 1H); 2.46 (s, 3H). 19F NMR (377 MHz, d6-DMSO) δ −139.21 (s, 1F); −127.41 (s, 1F).

Workup

  1. waitAfter 10 min
  2. customthe cooling bath was removed
  3. waitAfter 2 h
  4. additionHCl (5 N, 0.5 mL) was added
  5. additionEtOAc (10 mL) and saturated NH4Cl (10 mL) were added
  6. filtrationThe resulting emulsion was filtered through a glass frit
  7. dissolutionThe collected solid was dissolved in warm DMSO
  8. custompurified by prep HPLC (30-75% MeCN/water/w 0.1% TFA over 20 min)
  9. concentrationThe collected product fractions were concentrated to dryness
  10. additionSaturated NaHCO3 (10 mL) was added
  11. filtrationfiltered
  12. extractionThe filtrate was extracted with iPrOH (5%) in CHCl3 (3×5 mL)
  13. dry with materialThe combined organic layers were dried over Na2SO4
  14. concentrationconcentrated to a yellow solid which
  15. filtrationwas filtered as a suspension in ether

Sources & evidence

ORD record
ord-dcc43c8e565c474089ebfcfce4b600b1
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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