Trifluoroacetic acid → 1-{5-tert-butyl-2-[3-(3-hydroxy-propylamino)-phenyl]-2H-pyrazol-3-yl}-3-[4-(pyridin-4-yloxy)-phenyl]-urea

HRID 221899Notes

Reaction equation

HRID 221899 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:28][C:29]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([O:38][C:39]3[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=3)=[CH:34][CH:33]=2)=[O:30])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([NH:16][CH2:17][CH2:18][CH2:19][O:20][Si](C(C)(C)C)(C)C)[CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>CO.O.C(Cl)Cl>[C:1]([C:5]1[CH:6]=[C:7]([NH:28][C:29]([NH:31][C:32]2[CH:33]=[CH:34][C:35]([O:38][C:39]3[CH:40]=[CH:41][N:42]=[CH:43][CH:44]=3)=[CH:36][CH:37]=2)=[O:30])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([NH:16][CH2:17][CH2:18][CH2:19][OH:20])[CH:11]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 536301951-(5-tert-butyl-2-{3-[3-(tert-butyl-dimethyl-silanyloxy)-propylamino]-phenyl}-2H-pyrazol-3-yl)-3-[4-(pyridin-4-yloxy)-phenyl]-urea

Product 1

HCID 115696011-{5-tert-butyl-2-[3-(3-hydroxy-propylamino)-phenyl]-2H-pyrazol-3-yl}-3-[4-(pyridin-4-yloxy)-phenyl]-ureaYield 86.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(5-tert-butyl-2-{3-[3-(tert-butyl-dimethyl-silanyloxy)-propylamino]-phenyl}-2H-pyrazol-3-yl)-3-[4-(pyridin-4-yloxy)-phenyl]-urea (117 mg, 0.19 mmol) in methanol (2 mL) was added a solution of 10% TFA in H2O (2 mL). The reaction was stirred at room temperature overnight. The mixture was then diluted with DCM, basified by the addition of saturated aq NaHCO3 and extracted with DCM. The combined organic phases were washed with brine, dried over MgSO4, and concentrated at reduced pressure. The crude residue was purified by MPLC (eluting with 4% to 5.5% MeOH in DCM) to give 82 mg (86%) of the desired product 1-{5-tert-butyl-2-[3-(3-hydroxy-propylamino)-phenyl]-2H-pyrazol-3-yl}-3-[4-(pyridin-4-yloxy)-phenyl]-urea. 1H-NMR (DMSO-d6) δ 9.18 (s, 1H), 8.40 (dd, J=1.7 & 4.7 Hz, 2H), 8.32 (s, 1H), 7.48 (d, J=9.0 Hz, 2H), 7.17 (t, J=7.9 Hz, 1H), 7.07 (d, J=9.1 Hz, 2H), 6.85 (dd, J=1.5 & 4.7 Hz, 2H), 6.63-6.56 (m, 3H), 6.33 (s, 1H), 5.91 (t, J=5.3 Hz, 1H), 4.47 (t, J=5.1 Hz, 1H), 3.48 (q, J=6.1 Hz, 2H), 3.06 (q, J=6.6 Hz, 2H), 1.69 (quintet, J=6.5 Hz, 2H), 1.26 (s, 9H); MS LC-MS [M+H]+=501.2, RT=2.29 min.

Workup

  1. extractionextracted with DCM
  2. washThe combined organic phases were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated at reduced pressure
  5. customThe crude residue was purified by MPLC (eluting with 4% to 5.5% MeOH in DCM)

Sources & evidence

ORD record
ord-b98eb7c3a5e24990bd97cdf51f8340a0
Source dataset
uspto-grants-2012_06
Patent number
US08207166B2

Reaction notes

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