Trifluoroacetic acid → HCID 118272533, compound

HRID 590803Notes

Reaction equation

HRID 590803 reaction equation
[NH2:1][C:2]1[C:6]2[CH:7]=[N:8][C:9]([NH:11][C:12]([NH:14][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:16])=[O:13])=[CH:10][C:5]=2[N:4](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[N:3]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:1][C:2]1[C:6]2[CH:7]=[N:8][C:9]([NH:11][C:12]([NH:14][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:16])=[O:13])=[CH:10][C:5]=2[NH:4][N:3]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 118271680HCID 118271680, compound

Product 1

HCID 118272533HCID 118272533, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-1-(3-amino-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (310 mg, 0.576 mmol) and triethylsilane (184 μl, 1.151 mmol) in DCM (5232 μl) were treated with trifluoroacetic acid (2660 μl, 34.5 mmol) and stirred for 1 hr at room temperature. Reaction mixture was evaporated in vacuo, partioned between EtOAc/saturated aqeous NaHCO3 and extracted with EtOAc (2×). Combined organics were washed with saturated aqeous NaHCO3, brine, dried over Na2SO4 and evaporated in vacuo affording crude product which was purified by normal phase column chromotography eluting with MeOH/EtOAc (0-10%) affording (R)-1-(3-amino-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (145 mg, 0.489 mmol, 85% yield) as an off white solid. 1H NMR (500 MHz, dmso) δ 11.42 (s, 1H), 8.87 (s, 1H), 8.57 (s, 1H), 8.07 (s, 1H), 7.39-7.27 (m, 4H), 7.27-7.17 (m, 1H), 5.64 (s, 2H), 4.86 (m, 1H), 1.39 (d, 3H). MS ESI calc'd. For C15H16N6O[M+H]+ 297. found 297.

Workup

  1. customReaction mixture
  2. customwas evaporated in vacuo
  3. extractionextracted with EtOAc (2×)
  4. washCombined organics were washed with saturated aqeous NaHCO3, brine
  5. dry with materialdried over Na2SO4
  6. customevaporated in vacuo
  7. customaffording crude product which
  8. customwas purified by normal phase column chromotography
  9. washeluting with MeOH/EtOAc (0-10%)

Sources & evidence

ORD record
ord-ed3be0bbbc1146c6991bcb11cad1ad84
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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