4-Methylmorpholine → (R)-2-(3-(2-ethoxyphenoxy)piperidin-1-yl)-N-(3-iodobenzyl)pyrimidine-5-carboxamide

HRID 59908

Reaction equation

HRID 59908 reaction equation
[CH2:1]([O:3][C:4]1[CH:25]=[CH:24][CH:23]=[CH:22][C:5]=1[O:6][C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]2[N:18]=[CH:17][C:16]([C:19]([OH:21])=O)=[CH:15][N:14]=2)[CH2:8]1)[CH3:2].[I:26][C:27]1[CH:28]=[C:29]([CH2:33][NH2:34])[CH:30]=[CH:31][CH:32]=1.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>C1COCC1.CCOC(C)=O>[CH2:1]([O:3][C:4]1[CH:25]=[CH:24][CH:23]=[CH:22][C:5]=1[O:6][C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]2[N:14]=[CH:15][C:16]([C:19]([NH:34][CH2:33][C:29]3[CH:30]=[CH:31][CH:32]=[C:27]([I:26])[CH:28]=3)=[O:21])=[CH:17][N:18]=2)[CH2:8]1)[CH3:2]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 970123-IodobenzylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 118366221(R)-2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxylic acid

Product 1

HCID 118366187(R)-2-(3-(2-ethoxyphenoxy)piperidin-1-yl)-N-(3-iodobenzyl)pyrimidine-5-carboxamideYield 74%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (R)-2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxylic acid (2.00 g, 5.82 mmol), (3-iodophenyl)methanamine (1.00 mL, 7.20 mmol), N-methyl morpholine (2.00 mL, 18 mmol), EDCl (1.2 g, 5.9 mmol), and HOBT (455 mg, 2.91 mmol) in THF (30 mL) was stirred at room temperature overnight. The reaction was diluted with EtOAc (50 mL). The organic layer was washed with saturated aqueous solution of NH4Cl (50 mL), saturated aqueous solution of NaHCO3 (50 mL), and brine (50 mL), dried over Na2SO4 and concentrated to dryness. The residue was purified by flash column chromatography (0-50% EtOAc in Heptanes) to afford (R)-2-(3-(2-ethoxyphenoxy)piperidin-1-yl)-N-(3-iodobenzyl)pyrimidine-5-carboxamide (2.39 g, 74%) as a solid. 1H NMR (400 MHz, CDCl3) δ 8.69 (s, 2H), 7.69 (m, 1H), 7.64 (m, 1H), 7.32 (m, 1H), 7.10 (t, 1H), 6.98 (m, 2H), 6.88 (m, 2H), 6.13 (t, 1H), 4.58 (d, 2H), 4.48 (dd, 1H), 4.25 (m, 1H), 4.18 (m, 1H), 4.01 (m, 2H), 3.77 (dd, 1H), 3.64 (m, 1H), 2.13 (m, 1H), 1.97 (m, 2H), 1.59 (m, 1H), 1.39 (t, 3H). MS (ES+) 559.2 (M+H).

Workup

  1. washThe organic layer was washed with saturated aqueous solution of NH4Cl (50 mL), saturated aqueous solution of NaHCO3 (50 mL), and brine (50 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated to dryness
  4. customThe residue was purified by flash column chromatography (0-50% EtOAc in Heptanes)

Sources & evidence

ORD record
ord-781ec66446eb41ad9e344cf80ef7deef
Source dataset
uspto-grants-2016_09
Patent number
US09440949B2

Linked notes

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