Trifluoroacetic acid → HCID 118073643, compound

HRID 928155Notes

Reaction equation

HRID 928155 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4](Cl)[N:3]=1.[CH3:15][N:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:28]=[CH:27][C:25]([NH2:26])=[CH:24][CH:23]=2)[CH2:18][CH2:17]1.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(O)(C)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:26][C:25]2[CH:24]=[CH:23][C:22]([N:19]3[CH2:18][CH2:17][N:16]([CH3:15])[CH2:21][CH2:20]3)=[CH:28][CH:27]=2)[N:3]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 7372534-(4-Methylpiperazin-1-yl)anilineHCID 112184902,6-dichloro-9-(propan-2-yl)-9H-purine

Product 1

HCID 118073643HCID 118073643, compoundYield 86.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
78 °C

Procedure

To a reaction vial was added 2,6-dichloro-9-isopropyl-9H-purine (containing 6.3 mmol), 4-(4-methylpiperazin-1-yl)aniline (1.2 g, 6.3 mmol), isopropanol (32 mL, 0.2 M), and TFA (1 mL, 13 mmol). The reaction vial was capped, stirred and heated at 78° C. (block temperature) for 20 hr. The volatiles were removed to give a dark residue. Sat. aq. NaHCO3 (40 mL) was added. There was dark gummy solid precipitated out. Ethyl acetate (2×120 mL) and DCM (2×80 mL) were used to extract product. The combined organic layers were dried over Na2SO4 and evaporated to give a dark residue that was purified on silica with a gradient of 100% ethyl acetate to 10% ammonia (7 N in methanol)-90% ethyl acetate to give the title product as a light yellow solid (2.1 g, 86% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.04 (s, 1 H) 8.38 (s, 1 H) 7.61 (d, J=8.56 Hz, 2 H) 6.93 (d, J=8.93 Hz, 2 H) 4.71 (dt, J=13.39, 6.63 Hz, 1 H) 3.10 (br. s., 4 H) 2.45 (m, J=4.16 Hz, 4 H) 2.22 (s, 3 H) 1.52 (d, J=6.72 Hz, 6 H). m/z (APCI+) for C19H24ClN7 386.2 (M+H)+ with Cl isotope pattern. The regiochemistry of the product was also confirmed by small molecule X-ray crystallography.

Workup

  1. customThe reaction vial was capped
  2. customThe volatiles were removed
  3. customto give a dark residue
  4. customprecipitated out
  5. extractionto extract product
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. customevaporated
  8. customto give a dark residue that
  9. customwas purified on silica with a gradient of 100% ethyl acetate to 10% ammonia (7 N in methanol)-90% ethyl acetate

Sources & evidence

ORD record
ord-297c2395a92d454bab6a54d42bf33c19
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Reaction notes

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