Trifluoroacetic acid → HCID 11606207, compound

HRID 1174872Notes

Reaction equation

HRID 1174872 reaction equation
C([Si](C)(C)[O:6][CH2:7][CH2:8][N:9]([CH2:42][CH2:43][O:44][Si](C)(C)C(C)(C)C)[C:10]1[CH:11]=[C:12]([N:16]2[C:20]([NH:21][C:22]([NH:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][C:32]4[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=4)=[CH:27][CH:26]=3)=[O:23])=[CH:19][C:18]([C:38]([CH3:41])([CH3:40])[CH3:39])=[N:17]2)[CH:13]=[CH:14][CH:15]=1)(C)(C)C.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>CO.O.C(Cl)Cl>[OH:6][CH2:7][CH2:8][N:9]([CH2:42][CH2:43][OH:44])[C:10]1[CH:11]=[C:12]([N:16]2[C:20]([NH:21][C:22]([NH:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][C:32]4[CH:33]=[CH:34][N:35]=[CH:36][CH:37]=4)=[CH:27][CH:26]=3)=[O:23])=[CH:19][C:18]([C:38]([CH3:39])([CH3:40])[CH3:41])=[N:17]2)[CH:13]=[CH:14][CH:15]=1

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 53630196HCID 53630196, compound

Product 1

HCID 11606207HCID 11606207, compoundYield 36%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-[2-(3-amino-phenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(pyridin-4-yloxy)-phenyl]-urea (124 mg, 0.28 mmol), (tert-butyldimethylsilyloxy)acetaldehyde (135 mg, 0.70 mmol, 2.5 eq), and sodium triacetoxyborohydride (178 mg, 0.84 mmol, 3 eq) in anhydrous THF (2 mL) was added acetic acid (20 mg, 0.34 mmol, 1.2 eq). The reaction was stirred under N2 at room temperature for 2 h. The reaction mixture was quenched with saturated aq NaHCO3 and extracted with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4 and concentrated at reduced pressure. The residue was purified by MPLC (eluting with 45:55 to 65:35 EtOAc/hexanes) to give 153 mg (72%) of 1-[2-(3-{bis-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-amino}-phenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(pyridin-4-yloxy)-phenyl]-urea. 1H-NMR (DMSO-d6) δ 9.17 (s, 1H), 8.39 (d, J=6.3 Hz, 2H), 8.31 (s, 1H), 7.47 (d, J=9.0 Hz, 2H), 7.24 (t, J=7.9 Hz, 1H), 7.07 (d, J=9 Hz, 2H), 6.84 (d, J=6.1 Hz, 2H), 6.72-6.66 (m, 3H), 6.33 (s, 1H), 3.72 (t, J=5.8 Hz, 4H), 3.49 (t, J=5.9 Hz, 4H), 1.26 (s, 9H), 0.82 (s, 18H), −0.01 (s, 12H); MS LC-MS [M+H]+=760.3, RT=4.10 min. Step 2: To a solution of 1-[2-(3-{bis-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-amino}-phenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(pyridin-4-yloxy)-phenyl]-urea (153 mg, 0.20 mmol) in methanol (2 mL) was added a solution of 10% TFA in H2O (2 mL). The reaction was stirred at room temperature for 4 h. The mixture was then diluted with DCM, basified by addition of saturated NaHCO3 and extracted with DCM. The combined organic phases were washed with brine, dried over MgSO4, and concentrated at reduced pressure. The residue was purified by MPLC (eluting with 3% to 6% MeOH in DCM) to give 35 mg (36%) of the desired product. 1H-NMR (DMSO-d6) δ 9.17 (s, 1H), 8.40 (dd, J=1.5 & 4.7 Hz, 2H), 8.32 (s, 1H), 7.48 (d, J=8.8 Hz, 2H), 7.26-7.22 (m, 1H), 7.07 (d, J=9.1 Hz, 2H), 6.85 (dd, J=1.5 & 4.7 Hz, 2H), 6.71-6.69 (m, 2H), 6.63 (d, J=7.9 Hz, 1H), 6.34 (s, 1H), 4.76 (t, J=5.4 Hz, 2H), 3.54 (q, J=5.7 Hz, 4H), 3.43 (t, J=5.7 Hz, 4H), 1.26 (s, 9H); MS LC-MS [M+H]+=531.2, RT=2.27 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 residue was purified by MPLC (eluting with 3% to 6% MeOH in DCM)

Sources & evidence

ORD record
ord-6dbe8c0c0bfc473182ce4347ac126d4d
Source dataset
uspto-grants-2010_11
Patent number
US07838524B2

Reaction notes

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