3-Methoxypropylamine → HCID 46908438, compound

HRID 1631039Notes

Reaction equation

HRID 1631039 reaction equation
[Cl:1][C:2]1[C:3](O)=[N:4][CH:5]=[C:6]([C:8]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[CH3:25])=[C:15]([CH2:26][O:27][CH3:28])[CH:14]=3)[O:10][N:9]=2)[CH:7]=1.CCN(C(C)C)C(C)C.P(Cl)(Cl)(Cl)=O.[CH3:44][O:45][CH2:46][CH2:47][CH2:48][NH2:49]>C1(C)C=CC=CC=1.CC#N>[Cl:1][C:2]1[C:3]([NH:49][CH2:48][CH2:47][CH2:46][O:45][CH3:44])=[N:4][CH:5]=[C:6]([C:8]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[CH3:25])=[C:15]([CH2:26][O:27][CH3:28])[CH:14]=3)[O:10][N:9]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 16723-MethoxypropylamineHCID 24813Phosphorus oxychlorideHCID 81531Diisopropylethylamine2×HCID 178494467HCID 178494467, compound

Product 1

HCID 46908438HCID 46908438, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 3-chloro-5-(5-(2-(methoxymethyl)-2′-methylbiphenyl-4-yl)-1,2,4-oxadiazol-3-yl)pyridin-2-ol (0.702 g; 1.72 mmol) and DIEA (0.24 mL; 1.38 mmol) in toluene (30 mL) was added phosphorus oxychloride (0.192 mL; 2.06 mmol). The reaction mixture was heated at 120° C. for 2 hours. The solvent was removed in vacuo and the residue tritutrated with MeCN to afford a solid. A portion of the solid (0.150 g) combined with 3-methoxypropylamine (0.039 mL; 0.39 mmol) and DIEA (0.104 mL; 0.60 mmol) in MeCN (2 mL). The reaction mixture was heated under reflux for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash chromatography on silica, eluting with iso-hexane/EtOAc (100% iso-hexane to 100% EtOAc) to afford the title compound as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 8.84 (1 H, d, J=2.0 Hz), 8.40 (1 H, d, J=1.7 Hz), 8.20 (1 H, d, J=2.0 Hz), 8.15 (1 H, dd, J=7.9, 1.9 Hz), 7.36-7.23 (4 H, m), 7.13 (1 H, d, J=7.4 Hz), 6.03 (1 H, t, J=5.2 Hz), 4.22 (2 H, d, J=2.1 Hz), 3.67 (2 H, q, J=6.0 Hz), 3.58 (2 H, t, J=5.67 Hz), 3.40 (3 H, s), 3.32 (3 H, s), 2.08 (3 H, s), 2.01-1.92 (2 H, m). LC/MS: 479 (M+H)+. HPLC (Method E) Rt 5.76 min (Purity: 99.8%).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue tritutrated with MeCN to afford a solid
  3. temperatureThe reaction mixture was heated
  4. temperatureunder reflux for 18 hours
  5. customThe solvent was evaporated in vacuo
  6. customthe residue was purified by flash chromatography on silica
  7. washeluting with iso-hexane/EtOAc (100% iso-hexane to 100% EtOAc)

Sources & evidence

ORD record
ord-2d8176c948984ee59fa2e845806d1691
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

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