Trifluoroacetic acid → HCID 11656919, compound

HRID 1174863Notes

Reaction equation

HRID 1174863 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

4-{2-[4-(5-Amino-3-tert-butyl-pyrazol-1-yl)-phenoxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester was coupled with 4-(pyridin-3-yloxy)phenylamine by reaction with CDI in a similar manner to that described above, to provide the urea 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 (LC-MS [M+H]+=655, RT=3.51 min). Step 2. 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-e8309b3f089d42b588453c5f4dfcf008
Source dataset
uspto-grants-2010_11
Patent number
US07838524B2

Reaction notes

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