Triethylsilane → 1-[(1R)-1-(4-fluorophenyl)ethyl]-3-[3-(methylamino)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea

HRID 590795Notes

Reaction equation

HRID 590795 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][C:11]([NH:13][C:14]2[N:19]=[CH:18][C:17]3[C:20]([NH:42][CH3:43])=[N:21][N:22](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[C:16]=3[CH:15]=2)=[O:12])[CH3:9])=[CH:4][CH:3]=1.C([SiH](CC)CC)C>C(O)(C(F)(F)F)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][C:11]([NH:13][C:14]2[N:19]=[CH:18][C:17]3[C:20]([NH:42][CH3:43])=[N:21][NH:22][C:16]=3[CH:15]=2)=[O:12])[CH3:9])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 12052TriethylsilaneHCID 118272252(R)-1-(1-(4-fluorophenyl)ethyl)-3-(3-(methylamino)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea

Product 1

HCID 735043681-[(1R)-1-(4-fluorophenyl)ethyl]-3-[3-(methylamino)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

(R)-1-(1-(4-Fluorophenyl)ethyl)-3-(3-(methylamino)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (404 mg, 0.708 mmol) and triethylsilane (0.170 mL, 1.062 mmol) were stirred in TFA (5 mL) at room temperature for 30 min. The solvent was removed in vacuo, saturated NaHCO3 was added, and the products extracted into EtOAc (×2). The combined organic extracts were washed with brine, dried over Na2SO4, filtered through Celite, and concentrated in vacuo. Purification of the residue by flash chromatography (0-15% MeOH-EtOAc) gave 1-[(1R)-1-(4-fluorophenyl)ethyl]-3-[3-(methylamino)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea. MS ESI calc'd. For C16H17FN6O [M+1]+ 329. found 329. 1H NMR (500 MHz, DMSO-d6) δ 11.48 (s, 1H), 8.86 (s, 1H), 8.54 (s, 1H), 8.05 (br s, 1H), 7.36 (dd, J=8.5, 5.5 Hz, 2H), 7.24 (s, 1H), 7.14 (t, J=9.0 Hz, 2H), 6.25 (q, J=5.0 Hz, 1H), 4.88-4.83 (m, 1H), 2.81 (d, J=5.0 Hz, 3H), 1.38 (d, J=6.5 Hz, 3H).

Workup

  1. customThe solvent was removed in vacuo, saturated NaHCO3
  2. additionwas added
  3. extractionthe products extracted into EtOAc (×2)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered through Celite
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by flash chromatography (0-15% MeOH-EtOAc)

Sources & evidence

ORD record
ord-cb36ee6caf64493caeffc1e0e86bf856
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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