Ammonium Chloride → 1-(5-tert-Butyl-2-methyl-2H-pyrazol-3-yl)-3-{5-fluoro-2-[1-(2-hydroxy-2-methylpropyl)-1H-indazol-5-yloxy]-benzyl}-urea

HRID 1897526Notes

Reaction equation

HRID 1897526 reaction equation
[Si]([O:8][C:9]([CH3:44])([CH3:43])[CH2:10][N:11]1[C:19]2[C:14](=[CH:15][C:16]([O:20][C:21]3[CH:41]=[CH:40][C:39]([F:42])=[CH:38][C:22]=3[CH2:23][NH:24][C:25]([NH:27][C:28]3[N:29]([CH3:37])[N:30]=[C:31]([C:33]([CH3:36])([CH3:35])[CH3:34])[CH:32]=3)=[O:26])=[CH:17][CH:18]=2)[CH:13]=[N:12]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].[NH4+].[Cl-]>ClCCl>[C:33]([C:31]1[CH:32]=[C:28]([NH:27][C:25]([NH:24][CH2:23][C:22]2[CH:38]=[C:39]([F:42])[CH:40]=[CH:41][C:21]=2[O:20][C:16]2[CH:15]=[C:14]3[C:19](=[CH:18][CH:17]=2)[N:11]([CH2:10][C:9]([OH:8])([CH3:44])[CH3:43])[N:12]=[CH:13]3)=[O:26])[N:29]([CH3:37])[N:30]=1)([CH3:36])([CH3:34])[CH3:35]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 67411574HCID 67411574, compound

Product 1

HCID 426422141-(5-tert-Butyl-2-methyl-2H-pyrazol-3-yl)-3-{5-fluoro-2-[1-(2-hydroxy-2-methylpropyl)-1H-indazol-5-yloxy]-benzyl}-ureaYield 87.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of -(2-{1-[2-(tert-butyldimethylsilanyloxy)-2-methyl-propyl]-1H-indazol-5-yloxy}-5-fluorobenzyl)-3-(5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-urea (0.084 g, 0.135 mmol) in dichloromethane (3 mL) was added TBAF (0.70 mL of 1M in THF). The mixture was stirred at room temperature for 5 days. The reaction mixture was poured into NH4Cl and extracted with ethyl acetate (3×30 mL). The combined extracts were washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was chromatographed on silica eluting with acetone/hexanes (2:1) to afford 0.060 g of product (87% yield). MS (ESI+) m/z 509 (M+1) detected; 1H NMR (400 mHz, DMSO-D6) δ 8.45 (s, 1H), 7.98 (s, 1H), 7.74 (d, 1H), 7.17 (m, 3H), 7.08 (m, 1H), 6.85 (m, 2H), 5.95 (s, 1H), 4.66 (s, 1H), 4.33 (d, 2H), 4.30 (s, 2H), 2.50 (s, 3H), 1.18 (s, 9H), 1.12 (s, 6H).

Workup

  1. extractionextracted with ethyl acetate (3×30 mL)
  2. washThe combined extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was chromatographed on silica eluting with acetone/hexanes (2:1)

Sources & evidence

ORD record
ord-acfa1e74d70f4ef295a34ccce74fab3c
Source dataset
uspto-grants-2013_08
Patent number
US08518983B2

Reaction notes

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