Cesium carbonate → 4-(5-Chloro-2-(tetrahydro-2H-pyran-4-ylamino)pyridin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621667Notes

Reaction equation

HRID 1621667 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([NH2:7])[CH2:3][CH2:2]1.[Cl:8][C:9]1[CH:10]=[C:11]([C:16]2[N:21]=[C:20]([CH3:22])[N:19]=[C:18]([N:23]([CH2:33][C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=3)[CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)[N:17]=2)[C:12](F)=[N:13][CH:14]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([C:16]2[N:21]=[C:20]([CH3:22])[N:19]=[C:18]([N:23]([CH2:24][C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)[CH2:33][C:34]3[CH:35]=[CH:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=3)[N:17]=2)[C:12]([NH:7][CH:4]2[CH2:5][CH2:6][O:1][CH2:2][CH2:3]2)=[N:13][CH:14]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 4192234-AminotetrahydropyranHCID 666005044-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 666117944-(5-Chloro-2-(tetrahydro-2H-pyran-4-ylamino)pyridin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineYield 74.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of tetrahydro-2H-pyran-4-amine (130 mg, 1.285 mmol), 4-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (345 mg, 0.719 mmol), and cesium carbonate (165 mg, 0.506 mmol) in THF (2.5 mL) was heated under microwave irradiation (100° C., 15 min; 120° C., 2×15 min). The mixture was partitioned between EtOAc (10 mL) and water (5 mL). The organic layer was washed with water, saturated NH4Cl, dried over Na2SO4 and concentrated. The resulting solid was triturated with hot MeOH (10 mL) to give a yellow solid (300 mg). LCMS (ES, pos.): calcd for C30H33ClN6O3: 560.2. found: 561.2 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 9.48 (d, J=7.24 Hz, 1H); 8.67 (d, J=2.54 Hz, 1H); 8.13 (d, J=2.54 Hz, 1H); 7.18 (t, J=9.10 Hz, 4H); 6.87 (d, J=8.61 Hz, 4H); 4.82 (s, 2H); 4.77 (s, 2H); 4.17-4.29 (m, 1H); 3.91 (dt, J=11.74, 3.62 Hz, 2H); 3.81 (s, 3H); 3.80 (s, 3H); 3.55 (td, J=11.25, 1.96 Hz, 2H); 2.52 (s, 3H); 1.96 (br. s., 2H); 1.33-1.48 (m, 2H).

Workup

  1. customThe mixture was partitioned between EtOAc (10 mL) and water (5 mL)
  2. washThe organic layer was washed with water, saturated NH4Cl
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe resulting solid was triturated with hot MeOH (10 mL)

Sources & evidence

ORD record
ord-3bbcd8cb3e5e416fa5f86b12c532d011
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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