Trifluoroacetic acid → (S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(4-(hydroxymethyl)-3-methoxy-1H-pyrazolo[4,3-c]pyridin-6-yl)urea

HRID 588211Notes

Reaction equation

HRID 588211 reaction equation
[OH:1][C:2]([CH3:47])([CH3:46])[C@@H:3]([NH:10][C:11]([NH:13][C:14]1[N:19]=[C:18]([CH2:20][OH:21])[C:17]2[C:22]([O:44][CH3:45])=[N:23][N:24](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:16]=2[CH:15]=1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:1][C:2]([CH3:47])([CH3:46])[C@@H:3]([NH:10][C:11]([NH:13][C:14]1[N:19]=[C:18]([CH2:20][OH:21])[C:17]2[C:22]([O:44][CH3:45])=[N:23][NH:24][C:16]=2[CH:15]=1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 118271727(S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(4-(hydroxymethyl)-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea

Product 1

HCID 118271788(S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(4-(hydroxymethyl)-3-methoxy-1H-pyrazolo[4,3-c]pyridin-6-yl)urea

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(4-(hydroxymethyl)-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (533 mg, 0.849 mmol) was dissolved in DCM (3 ml), charged with triethylsilane (0.271 ml, 1.698 mmol) followed by TFA (3.27 ml, 42.5 mmol) and allowed to stir for 1 h at rt. The solvents were removed in vacuo and the residue was dissolved in 25 mL 10:1 EtOAc/MeOH and washed with 20 mL saturated sodium bicarbonate. The aq. was extracted 1×15 mL EtOAc and the combine organics were washed with brine, dried over sodium sulfate, concentrated vacuo and purified on silica gel 5-15% MeOH/DCM to provide (S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(4-(hydroxymethyl)-3-methoxy-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (110) as a white solid. MS: [M+H]+ m/z 386. 1H NMR (600 MHz, dmso) δ 12.00 (s, 1H), 9.20 (s, 1H), 7.31 (m, 2H), 7.25 (m, 2H), 7.15 (m, 1H), 7.07 (br s, 1H), 5.00 (t, J=6.0, 1H), 4.74 (d, J=6.0, 2H), 4.68 (s, 1H), 4.59 (d, J=9.0, 1H), 3.93 (s, 3H), 1.13 (s, 3H), 1.12 (s, 3H).

Workup

  1. customThe solvents were removed in vacuo
  2. dissolutionthe residue was dissolved in 25 mL 10:1 EtOAc/MeOH
  3. washwashed with 20 mL saturated sodium bicarbonate
  4. extractionThe aq. was extracted 1×15 mL EtOAc
  5. washthe combine organics were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated vacuo
  8. custompurified on silica gel 5-15% MeOH/DCM

Sources & evidence

ORD record
ord-f474f3f3fbe248e19c4cd6e0a04ab267
Source dataset
uspto-grants-2016_01
Patent number
US09226922B2

Reaction notes

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