Sodium Carbonate → 4-(5-(3,6-Dihydro-2H-pyran-4-YL)-2-fluoropyridin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1812379Notes

Reaction equation

HRID 1812379 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([N:16]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)[N:10]=2)[C:5]([F:8])=[N:6][CH:7]=1.[O:35]1[CH2:40][CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH2:37][CH2:36]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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]>[O:35]1[CH2:36][CH:37]=[C:38]([C:2]2[CH:3]=[C:4]([C:9]3[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([N:16]([CH2:26][C:27]4[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=4)[CH2:17][C:18]4[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=4)[N:10]=3)[C:5]([F:8])=[N:6][CH:7]=2)[CH2:39][CH2:40]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 666005044-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 666004024-(5-(3,6-Dihydro-2H-pyran-4-YL)-2-fluoropyridin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineYield 54.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 4-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (2.0 g, 4.17 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Frontier Scientific) (1.051 g, 5.00 mmol), Pd2(dba)3 (0.191 g, 0.208 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.199 g, 0.417 mmol) and 2 N Na2CO3 (5.21 mL, 10.42 mmol) in 10 mL of dioxane was heated in a microwave at 130° C. for 30 min. The reaction mixture was partitioned between 10 mL of 0.5 N NaOH and 50 mL of EtOAc. The organic layer was separated and washed with brine, dried and concentrated. The residue was purified on a silica gel column and eluted with 25 to 75% EtOAc in hexanes to give the title compound (1.19 g, 54% yield) as an off white crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.51-8.47 (m, 2H), 7.24 (t, J=9.2 Hz, 4H), 6.90 (m, 4H), 6.38 (m, 1H), 4.78 (s, 2H), 4.76 (s, 2H), 4.24 (d, J=2.7 Hz, 2H), 3.84 (m, 2H), 3.74 (s, 3H), 3.72 (s, 3H), 2.51 (m, 2H), 2.47 (s, 3H). m/z (ESI, positive ion) 528.0 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between 10 mL of 0.5 N NaOH and 50 mL of EtOAc
  2. customThe organic layer was separated
  3. washwashed with brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified on a silica gel column
  7. washeluted with 25 to 75% EtOAc in hexanes

Sources & evidence

ORD record
ord-fa59fa7c63d64bf0bddbfce4d37526cc
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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