Potassium Acetate → 4-(2-fluoro-5-(thiomorpholinomethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621702Notes

Reaction equation

HRID 1621702 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[N:3]=1.[F:28][C:29]1[C:34](B(O)O)=[CH:33][C:32]([CH2:38][N:39]2[CH2:44][CH2:43][S:42][CH2:41][CH2:40]2)=[CH:31][N:30]=1.C([O-])(=O)C.[K+]>CCO.O>[F:28][C:29]1[C:34]([C:2]2[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[CH2:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)[N:3]=2)=[CH:33][C:32]([CH2:38][N:39]2[CH2:44][CH2:43][S:42][CH2:41][CH2:40]2)=[CH:31][N:30]=1

Participants

6

Reactant 3

HCID 517044Potassium AcetateHCID 595482094-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineHCID 666002742-Fluoro-5-(thiomorpholinomethyl)pyridin-3-ylboronic acid

Product 1

HCID 666002434-(2-fluoro-5-(thiomorpholinomethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineYield 67.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (312 mg, 0.811 mmol), 2-fluoro-5-(thiomorpholinomethyl)pyridin-3-ylboronic acid (249 mg, 0.973 mmol), Am-Phos (40 mg, 0.057 mmol), and potassium acetate (239 mg, 2.432 mmol) in EtOH (3.5 mL) and water (1.5 mL) was heated in a microwave at 100° C. for 30 min. The mixture was partitioned between EtOAc (20 mL) and 1 N NaOH (3 mL). The separated EtOAc layer was washed with brine, concentrated and purified on a Redi-Sep pre-packed silica gel column (40 g) eluting with a gradient of 30-70% EtOAc in hexanes to give 4-(2-fluoro-5-(thiomorpholinomethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (306 mg, 67.3% yield) as a yellow viscous oil. 1H NMR (400 MHz) δ 8.47 (dd, J=9.3, 1.9 Hz, 1H); 8.28 (s, 1H); 7.24 (d, J=8.4 Hz, 4H); 6.90 (t, J=8.5 Hz, 4H); 4.76 (d, J=4.9Hz, 4H); 3.74 (s, 3H); 3.73 (s, 3H); 3.60 (s, 2H); 2.66-2.58 (m, 8H); 2.47 (s, 3H). m/z (ESI, +ve ion) 561 (M+H)+.

Workup

  1. customThe mixture was partitioned between EtOAc (20 mL) and 1 N NaOH (3 mL)
  2. washThe separated EtOAc layer was washed with brine
  3. concentrationconcentrated
  4. custompurified on a Redi-Sep pre-packed silica gel column (40 g)
  5. washeluting with a gradient of 30-70% EtOAc in hexanes

Sources & evidence

ORD record
ord-8d7804267d8a40f082c535448c14e10a
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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