Sodium Carbonate → tert-butyl 5-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-3,4-dihydro-1(2H)-pyridinecarboxylate

HRID 1619787Notes

Reaction equation

HRID 1619787 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[C:22]([O:23][CH3:24])[C:17]=3[N:16]=[C:15]2[CH:25]([F:27])[F:26])[N:3]=1.CC1(C)C(C)(C)OB([C:36]2[CH2:37][CH2:38][CH2:39][N:40]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH:41]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:26][CH:25]([F:27])[C:15]1[N:14]([C:4]2[N:5]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[N:7]=[C:2]([C:38]3[CH2:37][CH2:36][CH2:41][N:40]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH:39]=3)[N:3]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[C:22]([O:23][CH3:24])[C:17]=2[N:16]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 534881021-[4-Chloro-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazoleHCID 59327225tert-Butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 67545039tert-butyl 5-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-3,4-dihydro-1(2H)-pyridinecarboxylateYield 50%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (0.40 g, 1 mmol), tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydropyridine-1(2H)-carboxylate (0.382 g, 1.24 mmol), PdCl2(dppf) (63 mg), and 2 M aqueous Na2CO3 (8 mL) in dioxane (40 mL) was refluxed under nitrogen for 2 hrs. The dioxane was removed under vacuum and the residue was extracted into CH2Cl2. Chromatography on silica eluting with hexanes/EtOAc (8:2) gave 0.27 g (50% yield) of tert-butyl 5-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-3,4-dihydro-1(2H)-pyridinecarboxylate: 1H NMR (CDCl3) δ 8.59 (s, 1H), 7.99 (d, J=8.4 Hz, 1H), 7.60 (t, JHF=53.6 Hz, 1H), 7.34 (t, J=8.2 Hz, 1H), 6.81 (d, J=8.1 Hz, 1H), 4.04 (s, 3H), 4.02-3.75 (m, 8H), 3.71-3.64 (m, 2H), 2.56 (t, J=6.1 Hz, 2H), 2.00-1.91 (m, 2H), 1.57 (s, 9H).

Workup

  1. temperaturewas refluxed under nitrogen for 2 hrs
  2. customThe dioxane was removed under vacuum
  3. extractionthe residue was extracted into CH2Cl2

Sources & evidence

ORD record
ord-2f44d59ba8974385993ec48c9e76ef5d
Source dataset
uspto-grants-2014_07
Patent number
US08772287B2

Reaction notes

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