Trifluoroacetic acid → HCID 11656919, compound

HRID 221892Notes

Reaction equation

HRID 221892 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][O:16][C:17]2[CH:22]=[CH:21][C:20]([N:23]3[C:27]([NH:28][C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([O:38][C:39]5[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=5)=[CH:34][CH:33]=4)=[O:30])=[CH:26][C:25]([C:45]([CH3:48])([CH3:47])[CH3:46])=[N:24]3)=[CH:19][CH:18]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[C:45]([C:25]1[CH:26]=[C:27]([NH:28][C:29]([NH:31][C:32]2[CH:33]=[CH:34][C:35]([O:38][C:39]3[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=3)=[CH:36][CH:37]=2)=[O:30])[N:23]([C:20]2[CH:21]=[CH:22][C:17]([O:16][CH2:15][CH2:14][CH:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)=[CH:18][CH:19]=2)[N:24]=1)([CH3:48])([CH3:46])[CH3:47]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 11571048HCID 11571048, compound

Product 1

HCID 11656919HCID 11656919, compoundYield 26.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-{2-[4-(3-tert-butyl-5-{3-[4-(pyridin-3-yloxy)-phenyl]-ureido}-pyrazol-1-yl)-phenoxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester (210 mg, 0.32 mmol) in DCM (1 mL) was added trifluoroacetic acid (0.3 mL). The reaction mixture was stirred at room temperature for 16 h, concentrated at reduced pressure, re-dissolved in methanol and purified by preparative HPLC. The HPLC fraction containing the desired product was basified by addition of saturated aq Na2CO3 and then extracted with EtOAc. Evaporation of the solvent at reduced pressure gave the desired product 1-{5-tert-butyl-2-[4-(2-piperidin-4-yl-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-[4-(pyridin-3-yloxy)-phenyl]-urea (46.6 mg, 26%). 1H-NMR (DMSO-d6) δ 9.20 (s, 1H), 8.30 (m, 3H), 7.45-7.35 (m, 5H), 7.00 (m, 3H), 6.30 (s, 1H), 4.0 (m, 4H), 2.40 (m, 2H), 1.70-1.60 (m, 6H), 1.40 (s, 9H), 1.05 (m, 1H); MS LC-MS [M+H]+=555.3, RT=2.73 min.

Workup

  1. concentrationconcentrated at reduced pressure
  2. dissolutionre-dissolved in methanol
  3. custompurified by preparative HPLC
  4. additionThe HPLC fraction containing the desired product
  5. additionwas basified by addition of saturated aq Na2CO3
  6. extractionextracted with EtOAc
  7. customEvaporation of the solvent at reduced pressure

Sources & evidence

ORD record
ord-7c13ffdad4da482f8a2d3014b523d436
Source dataset
uspto-grants-2012_06
Patent number
US08207166B2

Reaction notes

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