Trifluoroacetic acid → HCID 178492159, compound

HRID 1621452Notes

Reaction equation

HRID 1621452 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[N:15]=[CH:14][C:13]([CH2:16][CH2:17][OH:18])=[CH:12][C:11]=2[C:19]2[N:27]=[C:26]([CH3:28])[N:25]=[C:24]3[C:20]=2[N:21]=[CH:22][N:23]3C2CCCCO2)=[CH:5][CH:4]=1.C(O)(C(F)(F)F)=O>CO>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[N:15]=[CH:14][C:13]([CH2:16][CH2:17][OH:18])=[CH:12][C:11]=2[C:19]2[N:27]=[C:26]([CH3:28])[N:25]=[C:24]3[C:20]=2[N:21]=[CH:22][NH:23]3)=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 665999832-(6-(6-Methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-YL)-9H-purin-6-YL)pyridin-3-YL)ethanol

Product 1

HCID 178492159HCID 178492159, compoundYield 35.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The crude 2-(6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethanol (193 mg, 0.418 mmol) was dissolved in MeOH (5.0 mL) and TFA (0.50 mL, 6.49 mmol) was added via syringe. The reaction was stirred at room temperature for 2.5 hours, and then more TFA (0.9 mL) was added, and stirring was continued overnight. Then, the flask was fitted with a reflux condenser and placed in a preheated oil bath (60° C.), stirring was continued for 75 minutes. (This 75 minute period was interrupted by an approximate 15 minute period where the flask was not in the oil bath.) The reaction was cooled to room temperature and filtered through a Celite® (diatomaceous earth) pad, which was washed with DCM and MeOH. The filtrate was concentrated and purified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min) to give 2-(6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9H-purin-6-yl)pyridin-3-yl)ethanol (56.0 mg, 35% yield over 2 steps). MS (ESI pos. ion) m/z 378 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.50 (s, 1H), 9.66 (s, 1H), 8.62 (s, 1H), 8.53 (s, 1H), 8.20-8.14 (m, 2H), 6.86 (d, J=8.8 Hz, 1H), 3.85 (s, 3H), 3.66 (t, J=6.86 Hz, 2H), 2.85 (s, 3H), 2.76 (t, J=6.86 Hz, 2H).

Workup

  1. stirringstirring
  2. waitwas continued overnight
  3. customThen, the flask was fitted with a reflux condenser
  4. customplaced in a preheated oil bath
  5. stirring(60° C.), stirring
  6. waitwas continued for 75 minutes
  7. wait(This 75 minute period was interrupted by an approximate 15 minute period
  8. temperature) The reaction was cooled to room temperature
  9. filtrationfiltered through a Celite® (diatomaceous earth) pad, which
  10. washwas washed with DCM and MeOH
  11. concentrationThe filtrate was concentrated
  12. custompurified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min)

Sources & evidence

ORD record
ord-ec2399f34cc2447db4571d0ef6c92793
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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