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

HRID 571393Notes

Reaction equation

HRID 571393 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[CH:20]=[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(O)(C(F)(F)F)=O.C([SiH](CC)CC)C>C(Cl)Cl>[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[CH:20]=[N:21][NH:22][C:16]=3[CH:15]=2)=[O:12])[CH3:9])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 12052Triethylsilane2×HCID 89526481(R)-1-(1-(4-fluorophenyl)ethyl)-3-(1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea

Product 1

HCID 71555394(R)-1-(1-(4-fluorophenyl)ethyl)-3-(1H-pyrazolo[4,3-c]pyridin-6-yl)ureaYield 12%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-1-(1-(4-fluorophenyl)ethyl)-3-(1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (157 mg, 0.291 mmol) in DCM (0.8 mL) was treated with TFA (0.2 mL) and triethylsilane (0.1 mL). The mixture was stirred at room temperature for 1.5 h. Additional TFA (0.2 mL) and triethylsilane (0.1 mL) were added and the mixture was stirred for 1.5 h and then evaporated in vacuo to afford a residue, which was purified by MS-directed reverse phase preparative-HPLC (C-18 stationary phase, eluting with a H2O/MeCN gradient with 0.1% TFA), to yield (R)-1-(1-(4-fluorophenyl)ethyl)-3-(1H-pyrazolo[4,3-c]pyridin-6-yl)urea (14 mg, 0.034 mmol, 12%). MS ESI calc'd. for C15H15FN5O [M+H]+ 300, found 300. 1H NMR (600 MHz, DMSO-d6) δ 9.22 (s, 1H), 8.15 (s, 1H), 7.92 (s, 1H), 7.32 (dd, J=8.5, 5.6 Hz, 2H), 7.12 (t, J=8.9 Hz, 2H), 7.07 (s, 1H), 6.78 (s, 1H), 4.79 (m, 1H), 1.35 (d, J=7.0 Hz, 3H).

Workup

  1. stirringthe mixture was stirred for 1.5 h
  2. customevaporated in vacuo
  3. customto afford a residue, which
  4. customwas purified by MS-directed reverse phase preparative-HPLC (C-18 stationary phase
  5. washeluting with a H2O/MeCN gradient with 0.1% TFA),

Sources & evidence

ORD record
ord-f137d97de92f4992aa6eaff89653f201
Source dataset
uspto-grants-2015_05
Patent number
US09023865B2

Reaction notes

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