Sodium Carbonate → tert-Butyl 4-(4-((2-(6-(4-(ethoxycarbonyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl)pyridin-2-yl)-4-methylphenoxy)methyl)phenyl)-3,6-dihydropyridine-1 (2H)-carboxylate

HRID 1891223Notes

Reaction equation

HRID 1891223 reaction equation
Br[C:2]1[CH:36]=[CH:35][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][C:9]=2[C:15]2[N:20]=[C:19]([N:21]3[C:25]([C:26]([F:29])([F:28])[F:27])=[C:24]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:23]=[N:22]3)[CH:18]=[CH:17][CH:16]=2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:45]2[CH2:46][CH2:47][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:49][CH:50]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(#N)C>[CH2:33]([O:32][C:30]([C:24]1[CH:23]=[N:22][N:21]([C:19]2[N:20]=[C:15]([C:9]3[CH:10]=[C:11]([CH3:14])[CH:12]=[CH:13][C:8]=3[O:7][CH2:6][C:5]3[CH:35]=[CH:36][C:2]([C:45]4[CH2:50][CH2:49][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][CH:46]=4)=[CH:3][CH:4]=3)[CH:16]=[CH:17][CH:18]=2)[C:25]=1[C:26]([F:29])([F:28])[F:27])=[O:31])[CH3:34]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 68489080Ethyl 1-(6-(2-((4-bromobenzyl)oxy)-5-methylphenyl)pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Product 1

HCID 86644574tert-Butyl 4-(4-((2-(6-(4-(ethoxycarbonyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl)pyridin-2-yl)-4-methylphenoxy)methyl)phenyl)-3,6-dihydropyridine-1 (2H)-carboxylate

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

A vial was charged with the title compound from Example 12 Step C (375 mg, 0.669 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (310 mg, 1.00 mmol; Tetrahedron Lett, 2000, 41, 3705-3708) and trans-dichlorobis(triphenylphosphine)palladium (II) (47 mg, 0.067 mmol). Acetonitrile (2.2 mL) and sodium carbonate (1.7 mL, 1.0 M aqueous, 1.7 mmol) were added, and the resulting mixture was degassed via nitrogen sparge. The reaction mixture was stirred at 70° C. for 15 h, then was allowed to cool to ambient temperature and was loaded directly onto a silica gel column. Purification by chromatography on silica gel (0 to 50% EtOAc in hexanes, then 50 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 663.0 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 8.15 (d, J=8.0 Hz, 1H), 8.12 (s, 1H), 7.86 (t, J=8.0 Hz, 1H), 7.79 (d, J=2.0 Hz, 1H), 7.51 (d, J=8.0 Hz, 1H), 7.36 (d, J=8.5 Hz, 2H), 7.32 (d, J=8.5 Hz, 2H), 7.16 (dd, J=8.5, 2.0 Hz, 1H), 6.95 (d, J=8.0 Hz, 1H), 6.08-6.02 (m, 1H), 5.11 (s, 2H), 4.39 (q, J=7.0 Hz, 2H), 4.08-4.06 (m, 2H), 3.65-3.63 (m, 2H), 2.54-2.50 (m, 2H), 2.35 (s, 3H), 1.49 (s, 9H), 1.41 (q, J=7.0 Hz, 3H).

Workup

  1. customthe resulting mixture was degassed via nitrogen
  2. customsparge
  3. temperatureto cool to ambient temperature
  4. customPurification by chromatography on silica gel (0 to 50% EtOAc in hexanes

Sources & evidence

ORD record
ord-773cb14c7c084dec919c1605f655588f
Source dataset
uspto-grants-2013_08
Patent number
US08507512B2

Reaction notes

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