Tetrabutylammonium Fluoride → 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(3-hydroxymethyl-4-methyl-piperazin-1-ylmethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea

HRID 1402195Notes

Reaction equation

HRID 1402195 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:17][C:18]([NH:20][C@@H:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C@H:24]([O:31][C:32]3[CH:33]=[CH:34][C:35]4[N:36]([C:38]([CH2:41][N:42]5[CH2:47][CH2:46][N:45]([CH3:48])[CH:44]([CH2:49][O:50][Si](C(C)C)(C(C)C)C(C)C)[CH2:43]5)=[N:39][N:40]=4)[CH:37]=3)[CH2:23][CH2:22]2)=[O:19])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.O>[C:1]([C:5]1[CH:6]=[C:7]([NH:17][C:18]([NH:20][C@@H:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C@H:24]([O:31][C:32]3[CH:33]=[CH:34][C:35]4[N:36]([C:38]([CH2:41][N:42]5[CH2:47][CH2:46][N:45]([CH3:48])[CH:44]([CH2:49][OH:50])[CH2:43]5)=[N:39][N:40]=4)[CH:37]=3)[CH2:23][CH2:22]2)=[O:19])[N:8]([C:10]2[CH:11]=[CH:12][C:13]([CH3:16])=[CH:14][CH:15]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86687057HCID 86687057, compound

Product 1

HCID 716037301-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(3-hydroxymethyl-4-methyl-piperazin-1-ylmethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureaYield 51%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of Intermediate 56f (60.0 mg, 72.0 μmol) and TBAF (1M in THF, 144 μL, 144 μmol) in THF (3 mL) was stirred at RT for 1 h. The mixture was diluted with water and extracted with EtOAc (3×). The combined organic extracts were washed with brine, and concentrated in vacuo. The residue was purified by FCC, using 0-20% MeOH in DCM, to afford the title compound as an off-white solid (24.9 mg, 51%). LCMS (Method 5): Rt 3.54 min, m/z 678 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.27 (9H, s), 1.82-2.01 (4H, m), 2.01-2.25 (7H, m), 2.53-2.88 (3H, m), 3.21 (1H, m), 3.54 (1H, m), 3.96-4.11 (2H, m), 4.37 (1H, dt, J 12.5, 5.4), 4.84 (1H, m), 5.47 (1H, m), 6.32 (1H, s), 7.10 (1H, d, J 8.4), 7.22-7.44 (9H, m), 7.72 (1H, d, J 10.3), 8.02 (1H, s), 8.30 (1H, m).

Workup

  1. extractionextracted with EtOAc (3×)
  2. washThe combined organic extracts were washed with brine
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-ed531742874a4634b0d84604f3473d11
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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