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Triethylamine → 4-(3-(5-cyclopropylpyridin-2-yloxy)benzylidene)-N-(pyridin-3-yl)piperidine-1-carboxamide

HRID 1666385
Notes
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Reaction equation

HRID 1666385 reaction equation
FC(F)(F)C(O)=O.[CH:8]1([C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([CH:24]=[C:25]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)[CH:19]=3)=[N:15][CH:16]=2)[CH2:10][CH2:9]1.[N:31]1[CH:36]=[CH:35][CH:34]=[C:33]([NH:37][C:38](=O)[O:39]C2C=CC=CC=2)[CH:32]=1.C(N(CC)CC)C>CS(C)=O>[CH:8]1([C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]3[CH:19]=[C:20]([CH:21]=[CH:22][CH:23]=3)[CH:24]=[C:25]3[CH2:30][CH2:29][N:28]([C:38]([NH:37][C:33]4[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=4)=[O:39])[CH2:27][CH2:26]3)=[N:15][CH:16]=2)[CH2:10][CH2:9]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 6935890Phenyl pyridin-3-ylcarbamateHCID 668761235-Cyclopropyl-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine trifluoroacetate

Product 1

HCID 249640604-(3-(5-cyclopropylpyridin-2-yloxy)benzylidene)-N-(pyridin-3-yl)piperidine-1-carboxamideYield 58%

Reagents, catalysts & solvents 1

HCID 679
Dimethyl Sulfoxide
Solvent

Conditions

Temperature
60 °C

Procedure

To a solution of 5-cyclopropyl-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine trifluoroacetate (125 mg, 0.408 mmol) in DMSO (5 mL) was added phenyl pyridin-3-ylcarbamate (87.4 mg, 0.408 mmol) followed by triethylamine (0.12 mL, 0.82 mmol). The reaction was heated to 60° C. overnight and then allowed to cool to RT. The reaction mixture was partitioned between EtOAc and water. The organic layer was dried and concentrated. Purification by silica gel column chromatography (0-5% MeOH/CH2Cl2) afforded the title compound as a white foam (101 mg, 58% yield). MS (APCI 10V) AP+2 427.07; 1H NMR (400 MHz, CDCl3) δ ppm 0.61-0.66 (m, 2H) 0.93-0.99 (m, 2H) 1.55 (s, 1H) 1.81-1.89 (m, 1H) 2.45 (t, 2H) 2.58 (t, 2H) 3.50 (t, 2H) 3.60 (t, 2H) 6.38 (s, 1H) 6.44 (s, 1H) 6.80 (d, 1H) 6.94 (br. s., 1H) 6.96-7.01 (m, 2H) 7.20-7.23 (m, 1H) 7.29-7.35 (m, 2H) 7.99-8.01 (m, 1H) 8.26 (d, 1H) 8.42 (d, 1H).

Workup

  1. temperatureto cool to RT
  2. customThe reaction mixture was partitioned between EtOAc and water
  3. customThe organic layer was dried
  4. concentrationconcentrated
  5. customPurification by silica gel column chromatography (0-5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-4b2e27eebfde4dcf8147abd79e9286b2
Source dataset
uspto-grants-2011_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08044052B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes