Tetrabutylammonium Fluoride → 1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[(1S,4R)-4-[[3-(4-hydroxypiperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]oxy]-1,2,3,4-tetrahydronaphthalen-1-yl]urea

HRID 2284960Notes

Reaction equation

HRID 2284960 reaction equation
CCCC[N+:5](CCCC)(CCCC)CCCC.[F-].[C:19]([C:23]1[CH:24]=[C:25]([NH:35][C:36]([NH:38][C@@H:39]2[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[C@H:42]([O:49][C:50]3[CH:51]=[CH:52][C:53]4[N:54]([C:56]([N:59]5[CH2:64][CH2:63][CH:62]([O:65][Si](C(C)C)(C(C)C)C(C)C)[CH2:61][CH2:60]5)=[N:57][N:58]=4)[CH:55]=3)[CH2:41][CH2:40]2)=[O:37])[N:26]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)[N:27]=1)([CH3:22])([CH3:21])[CH3:20]>C1COCC1>[NH4+:5].[OH-:37].[C:19]([C:23]1[CH:24]=[C:25]([NH:35][C:36]([NH:38][C@@H:39]2[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[C@H:42]([O:49][C:50]3[CH:51]=[CH:52][C:53]4[N:54]([C:56]([N:59]5[CH2:64][CH2:63][CH:62]([OH:65])[CH2:61][CH2:60]5)=[N:57][N:58]=4)[CH:55]=3)[CH2:41][CH2:40]2)=[O:37])[N:26]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)[N:27]=1)([CH3:22])([CH3:20])[CH3:21]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 89623737HCID 89623737, compound

Product 2

HCID 14923Ammonium HydroxideYield 0.1%HCID 896121481-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[(1S,4R)-4-[[3-(4-hydroxypiperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]oxy]-1,2,3,4-tetrahydronaphthalen-1-yl]ureaYield 154.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

TBAF (1M in THF, 0.235 mL, 0.235 mmol) was added dropwise to a solution of Intermediate 24f (124 mg, 0.157 mmol) in dry THF (3 mL) at −30° C. for 4 h under N2. The mixture was allowed to warm to RT, then stirred for 5 h. The solution was applied to an SCX-2 cartridge and washed with MeOH. The product was eluted with 2M NH3 in MeOH; concentration in vacuo left a brown foam. HPLC (Gemini C18; 40-90% MeCN in H2O, 0.1% NH4OH) gave the title compound as a white powder (77 mg, 77%). LCMS (Method 5): Rt 4.18 min, m/z 635 [MH+]. NMR (400 MHz, CDCl3): 1.33 (9H, s), 1.71-1.80 (2H, m), 1.87-1.96 (1H, m), 2.01-2.12 (4H, m), 2.25 (1H, m), 2.36 (3H, s), 3.04-3.11 (2H, m), 3.37-3.44 (2H, m), 3.93 (1H, m), 5.09 (1H, td, J 8.9, 5.3), 5.19 (1H, t, J 4.0), 5.44 (1H, d, J 8.8), 6.28 (1H, s), 6.46 (1H, br s), 6.99 (1H, dd, J 9.9, 2.1), 7.21 (2H, d, J 8.1), 7.25-7.33 (5H, m), 7.39 (2H, d, J 8.1), 7.49 (1H, d, J 9.9).

Workup

  1. washwashed with MeOH
  2. washThe product was eluted with 2M NH3 in MeOH
  3. concentrationconcentration in vacuo
  4. waitleft a brown foam

Sources & evidence

ORD record
ord-68fb2ca2f6a941d7819075a8d4d89c11
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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