Tetrabutylammonium Fluoride → 1-[5-tert-Butyl-2-(3-hydroxy-phenyl)-2H-pyrazol-3-yl]-3-[(1S,4R)-4-(3-isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea

HRID 75604Notes

Reaction equation

HRID 75604 reaction equation
CCCC[N+](CCCC)(CCCC)CCCC.[F-].[C:19]([C:23]1[CH:24]=[C:25]([NH:45][C:46]([NH:48][C@@H:49]2[C:58]3[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=3)[C@H:52]([O:59][C:60]3[CH:61]=[CH:62][C:63]4[N:64]([C:66]([CH:69]([CH3:71])[CH3:70])=[N:67][N:68]=4)[CH:65]=3)[CH2:51][CH2:50]2)=[O:47])[N:26]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([O:34][Si](C(C)C)(C(C)C)C(C)C)[CH:29]=2)[N:27]=1)([CH3:22])([CH3:21])[CH3:20]>C1COCC1>[C:19]([C:23]1[CH:24]=[C:25]([NH:45][C:46]([NH:48][C@@H:49]2[C:58]3[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=3)[C@H:52]([O:59][C:60]3[CH:61]=[CH:62][C:63]4[N:64]([C:66]([CH:69]([CH3:71])[CH3:70])=[N:67][N:68]=4)[CH:65]=3)[CH2:51][CH2:50]2)=[O:47])[N:26]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([OH:34])[CH:29]=2)[N:27]=1)([CH3:22])([CH3:21])[CH3:20]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 866867031-[5-tert-Butyl-2-(3-triisopropylsilanyloxy-phenyl)-2H-pyrazol-3-yl]-3-[(1S,4R)-4-(3-isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea

Product 1

HCID 866867021-[5-tert-Butyl-2-(3-hydroxy-phenyl)-2H-pyrazol-3-yl]-3-[(1S,4R)-4-(3-isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-ureaYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

TBAF (1M in THF, 350 μL, 0.35 mmol) was added to a solution of Intermediate 22c (258 mg, 0.35 mmol) in THF (5.0 mL) at 0° C. The reaction was stirred for 1 h then partitioned between EtOAc and water. The aqueous layer was then extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-10% MeOH in DCM, to give the title compound as an off-white solid (150 mg, 75%). LCMS (Method 1): Rt 4.11 min, m/z 580 [MH+]. 1H NMR (400 MHz, d4-MeOD): 1.30 (9H, s), 1.42 (3H, d, J 6.9), 1.45 (3H, d, J 6.9), 1.88-2.16 (3H, m), 2.20-2.30 (1H, m), 3.51 (1H, sept, J 6.9), 4.90 (1H, dd, J 8.9, 5.6), 5.45 (1H, t, J 4.1), 6.33 (1H, s), 6.84 (1H, ddd, J 8.3, 2.6, 0.8), 6.88-6.94 (2H, m), 7.19-7.26 (2H, m), 7.26-7.33 (4H, m), 7.61 (1H, d, J 10.0), 8.01 (1H, s).

Workup

  1. customthen partitioned between EtOAc and water
  2. extractionThe aqueous layer was then extracted with EtOAc (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-1fec5a8dbbdb48fb9b9d9f789acfc0ff
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

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