Pyridine → HCID 57438705, compound

HRID 2354511Notes

Reaction equation

HRID 2354511 reaction equation
Cl.[C:2]([C:4]1[CH:5]=[C:6]([C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)[C@@H:11]([NH2:13])[CH3:12])[CH:7]=[CH:8][CH:9]=1)#[N:3].[CH3:22][C:23]([O:28][C:29]1[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][N:30]=1)([CH3:27])[C:24](O)=[O:25].Cl.C(N=C=NCCCN(C)C)C.N1C=CC=CC=1>C(#N)C>[C:2]([C:4]1[CH:5]=[C:6]([CH:10]([CH2:14][C:15]2[CH:16]=[CH:17][C:18]([OH:21])=[CH:19][CH:20]=2)[CH:11]([NH:13][C:24](=[O:25])[C:23]([O:28][C:29]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][N:30]=2)([CH3:27])[CH3:22])[CH3:12])[CH:7]=[CH:8][CH:9]=1)#[N:3]

Participants

6

Reactant 4

HCID 1049PyridineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 16748320HCID 16748320, compoundHCID 16748323HCID 16748323, compound

Product 1

HCID 57438705HCID 57438705, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of N-(1S, 2S)-[2-(3-cyanophenyl)-3-(4-hydroxyphenyl)-1-methylpropyl]amine hydrochloride (Reference Example 8, 0.17 g, 0.49 mmol), 2-methyl-2-(5-methyl-2-pyridyloxy)propionic acid (Reference Example 12, 96 mg, 0.49 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (0.11 g, 0.59 mmol) in acetonitrile (2 mL) at 0° C. was added pyridine (91 uL, 1.1 mmol). The reaction was allowed to warm up to room temperature overnight, and was quenched with saturated with sodium bicarbonate (2 mL). The resulting mixture was partitioned between tert-butyl methyl ether (20 mL) and water (20 mL). The organic layer was separated, washed with 1 M hydrochloric acid, water and brine and concentrated to dryness. The residue was purified by flash column chromatography on silica gel eluting with 10 to 70% ethyl acetate in hexane to afford N-[2-(3-Cyano-phenyl)-3-(4-hydroxyphenyl)-1-methylpropyl]-2-(5-methyl-2-pyridyloxy)-2-methylpropanamide. 1H NMR (500 MHz, CD3OD): δ 7.85 (br d, 1H), 7.81 (d, 1H), 7.53-7.80 (m, 2H), 7.38 (t, 1H), 7.34 (br d, 1H), 7.32 (br s, 1H), 6.80 (d, 1H), 6.51 (ABq, 4H), 4.26 (m, 1H), 3.01 (dd, 1H), 2.81 (td, 1H), 2.54 (dd, 1H), 2.12 (s, 3H), 1.73 (s, 3H), 1.67 (s, 3H), 0.83 (d, 3H). LC-MS: m/e 444 (M+H)+ (3.3 min).

Workup

  1. customwas quenched with saturated with sodium bicarbonate (2 mL)
  2. customThe resulting mixture was partitioned between tert-butyl methyl ether (20 mL) and water (20 mL)
  3. customThe organic layer was separated
  4. washwashed with 1 M hydrochloric acid, water and brine
  5. concentrationconcentrated to dryness
  6. customThe residue was purified by flash column chromatography on silica gel eluting with 10 to 70% ethyl acetate in hexane

Sources & evidence

ORD record
ord-9c72ab7e27694a0298058b325e945f49
Source dataset
uspto-grants-2010_07
Patent number
US07754188B2

Reaction notes

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