Ethyl Acetate → 4-Chloro-N-{2-[4-(difluoromethoxy)phenyl]ethyl}-6-methoxy-1,3,5-triazin-2-amine

HRID 517482

Reaction equation

HRID 517482 reaction equation
Cl[C:2]1[N:7]=[C:6]([Cl:8])[N:5]=[C:4]([O:9][CH3:10])[N:3]=1.CCN(C(C)C)C(C)C.[F:20][CH:21]([F:32])[O:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][NH2:31])=[CH:25][CH:24]=1.CCOC(C)=O>C(#N)C.O>[Cl:8][C:6]1[N:5]=[C:4]([O:9][CH3:10])[N:3]=[C:2]([NH:31][CH2:30][CH2:29][C:26]2[CH:25]=[CH:24][C:23]([O:22][CH:21]([F:20])[F:32])=[CH:28][CH:27]=2)[N:7]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 192672,4-Dichloro-6-methoxy-3,5-triazineHCID 81531DiisopropylethylamineHCID 49622922-(4-(Difluoromethoxy)phenyl)ethan-1-amine

Product 1

HCID 896197934-Chloro-N-{2-[4-(difluoromethoxy)phenyl]ethyl}-6-methoxy-1,3,5-triazin-2-amineYield 31.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of 1.8 g of 2,4-dichloro-6-methoxy-1,3,5-triazine in 40 ml of acetonitrile is cooled on an ice bath, 1.28 ml of DIPEA and then 1.68 g of 2-[4-(difluoromethoxy)phenyl]ethanamine are added and the mixture is stirred for 30 minutes. The reaction mixture is diluted by adding 100 ml of EtOAc and 50 ml of water, the phases are separated by settling, the organic phase is washed with saturated NaCl solution and dried over MgSO4, and the solvent is evaporated off under vacuum. The residue is taken up in DCM, the insoluble matter is filtered off and the filtrate is concentrated under vacuum. The residue is chromatographed on silica gel, eluting with a cyclohexane/EtOAc mixture in a gradient of from (95/5 v/v) to (80/20 v/v). 0.94 g of the expected compound is obtained.

Workup

  1. additionThe reaction mixture is diluted
  2. customthe phases are separated
  3. washthe organic phase is washed with saturated NaCl solution
  4. dry with materialdried over MgSO4
  5. customthe solvent is evaporated off under vacuum
  6. filtrationthe insoluble matter is filtered off
  7. concentrationthe filtrate is concentrated under vacuum
  8. customThe residue is chromatographed on silica gel
  9. washeluting with a cyclohexane/EtOAc mixture in a gradient of from (95/5 v/v) to (80/20 v/v)

Sources & evidence

ORD record
ord-b9beb49da07947d8883b89d17e513bab
Source dataset
uspto-grants-2015_08
Patent number
US09115121B2

Linked notes

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