5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine → HCID 58102779, compound

HRID 450185Notes

Reaction equation

HRID 450185 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[CH:37]=[CH:38][C:39]([NH2:42])=[N:40][CH:41]=2)O1>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].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:36]3[CH:37]=[CH:38][C:39]([NH2:42])=[N:40][CH:41]=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 2

HCID 27565555-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 534881021-[4-Chloro-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole

Product 1

HCID 58102779HCID 58102779, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 0.30 g (0.75 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole, 0.21 g (0.95 mmol) of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinamine, and 0.057 g (0.08 mmol) of PdCl2(dppf) in a mixture of 1,4-dioxane (30 mL) and 2M Na2CO3 solution (6 mL) was heated at 100° C. for 5 hrs under nitrogen. After cooling, the mixture was concentrated, diluted with water, and extracted with EtOAc (×4). The organic layer was washed with brine, dried (Na2SO4), and concentrated. Chromatography on silica, eluting first with CH2Cl2-EtOAc (3:1) and then with CH2Cl2-EtOAc (1:3), gave an off-white powder, which was recrystallized from CH2Cl2/EtOH to give 0.144 g (43% yield) of 5-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-pyridinamine: mp 259-261° C.; 1H NMR (DMSO-d6) δ9.04 (d, J=2.2 Hz, 1H), 8.32 (dd, J=8.8, 2.4 Hz, 1H), 8.04 (d, J=8.3 Hz, 1H), 7.79 (t, JHF=52.8 Hz, 1H), 7.47 (t, J=8.2 Hz, 1H), 6.99 (d, J=7.9 Hz, 1H), 6.85 (s, 2H), 6.57 (d, J=8.8 Hz, 1H), 4.04-4.00 (m, 5H), 3.89 (br s, 2H), 3.76 (s, 4H); Anal. Calcd. for C21H20F2N8O20.49H2O: C, 54.45; H, 4.6; N, 24.2. Found: C, 54.8; H, 4.2; N, 24.2%.

Workup

  1. temperatureAfter cooling
  2. concentrationthe mixture was concentrated
  3. additiondiluted with water
  4. extractionextracted with EtOAc (×4)
  5. washThe organic layer was washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. washChromatography on silica, eluting first with CH2Cl2-EtOAc (3:1)
  9. customwith CH2Cl2-EtOAc (1:3), gave an off-white powder, which
  10. customwas recrystallized from CH2Cl2/EtOH

Sources & evidence

ORD record
ord-4184d4837f704fcb9f5bf0320f62c6f1
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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