Methylamine → [3-(1-Ethylpropoxy)-6-(2-methoxy-4-trifluoromethoxyphenyl)-5-methylpyridin-2-yl]-methylamine

HRID 1354240Notes

Reaction equation

HRID 1354240 reaction equation
Cl[C:2]1[C:7]([O:8][CH:9]([CH2:12][CH3:13])[CH2:10][CH3:11])=[CH:6][C:5]([CH3:14])=[C:4]([C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][C:16]=2[O:26][CH3:27])[N:3]=1.P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.[CH3:41][NH2:42].CC([O-])(C)C.[K+]>C1(C)C=CC=CC=1.CCOC(C)=O.CCCCCC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:10]([CH:9]([O:8][C:7]1[C:2]([NH:42][CH3:41])=[N:3][C:4]([C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][C:16]=2[O:26][CH3:27])=[C:5]([CH3:14])[CH:6]=1)[CH2:12][CH3:13])[CH3:11]

Participants

9

Reactant 4

HCID 6329MethylamineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 211047772-Chloro-3-(1-ethylpropoxy)-6-(2-methoxy-4-trifluoromethoxyphenyl)-5-methylpyridineHCID 23665647Potassium tert-butoxide

Product 1

HCID 21104805[3-(1-Ethylpropoxy)-6-(2-methoxy-4-trifluoromethoxyphenyl)-5-methylpyridin-2-yl]-methylamine

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

Pd2dba3 (4 mg) is added to a solution of compound 45 (70 mg, 0.173 mmol) in toluene (1 ml), followed by the addition of P(t-Bu)3 (1.4 mg), methylamine (2M in THF, 0.17 ml, 0.347 mmol) and t-BuOK (1M in THF, 0.26 ml, 0.26 mmol). The resulting mixture is sealed and heated to 55° C. overnight, then cooled to room temperature. The reaction mixture is diluted with 30% EtOAc in hexane, washed with water, brine, dried, filtered and evaporated. The crude product is purified by chromatograph (eluted with 6% EtOAc in hexane) to give the product 48 as a light yellow solid. 1H NMR (CDCl3) δ 0.97 (t, J=7.6 Hz, 6H), 1.71 (m, 4H), 1.98 (s, 3H), 2.99 (s, 3H), 3.79 (s, 3H), 4.13 (m, 1H), 4.77 (brs, 1H), 6.67 (s, 1H), 6.77 (s, 1H), 6.87 (dd, 1H), 7.32 (d, J=8.4 Hz, 1H). LCMS 399.4 (M+1).

Workup

  1. customThe resulting mixture is sealed
  2. temperaturecooled to room temperature
  3. washwashed with water, brine
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product is purified by chromatograph (eluted with 6% EtOAc in hexane)

Sources & evidence

ORD record
ord-4963a40a2456408780602a86958f0815
Source dataset
uspto-grants-2007_05
Patent number
US07223778B2

Reaction notes

Loading…