HCID 49780166, compound → HCID 86686192, compound

HRID 929508Notes

Reaction equation

HRID 929508 reaction equation
C([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]([N:17]2[CH2:22][CH2:21][CH:20]([NH:23][C:24]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=3)=[O:25])[CH2:19][CH2:18]2)=[O:16])[CH2:10][CH2:9]1)C1C=CC=CC=1>C(O)C.[Pd]>[N:11]1([CH2:14][C:15]([N:17]2[CH2:18][CH2:19][CH:20]([NH:23][C:24]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][C:34]([F:37])([F:35])[F:36])=[CH:29][CH:28]=3)=[O:25])[CH2:21][CH2:22]2)=[O:16])[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1

Participants

4

Reactant 1

HCID 49780166HCID 49780166, compound

Product 1

HCID 86686192HCID 86686192, compoundYield 114.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

Compound 50 (110 mg, 0.21 mmol) was deprotected by stirring overnight with 10% Pd/C in ethanol (15 mL) under a hydrogen atmosphere. The reaction was filtered through a bed of celite and the filtrate evaporated to give intermediate 1-(1-((piperazin-1-yl)acetyl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (103 mg, quantitative) as a clear oil, which was used without purification and coupled with acetic acid by Method E. Flash chromatography eluted with 9:1 DCM:MeOH and recrystallization from EtOAc:hexanes afforded compound 51 (73 mg, 74% over 2 steps) as a white solid: Mp 111-122° C. 1H NMR (500 MHz, DMSO-d6) δ 8.52 (s, 1H), 7.47 (d, J=8.9 Hz, 2H), 7.22 (d, J=8.6 Hz, 2H), 6.25 (d, J=7.7 Hz, 1H), 4.15 (d, J=13.1 Hz, 1H), 3.92 (d, J=13.2 Hz, 1H), 3.76-3.67 (m, 1H), 3.47-3.38 (m, 4H), 3.25 (d, J=13.5 Hz, 1H), 3.12 (q, J=13.0 Hz, 2H), 2.81 (t, J=11.5 Hz, 1H), 2.37-2.32 (m, 2H), 1.98 (s, 3H), 2.44-2.40 (m, 2H), 1.90-1.77 (m, 2H), 1.42-1.31 (m, 1H), 1.26-1.15 (m, 1H). Purity 90%. HRMS calculated for C20H21F3N4O3−H+ 470.2015. found (ESI(−), [M−H]) 470.2009.

Workup

  1. filtrationThe reaction was filtered through a bed of celite
  2. customthe filtrate evaporated

Sources & evidence

ORD record
ord-9da491d72f814c149ef33c1e8e9771ab
Source dataset
uspto-grants-2016_03
Patent number
US09296693B2

Reaction notes

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