Water → 6-chloro-N-(3-chloro-4-methoxyphenyl)-N'-cycloheptyl-[1,3,5]triazine-2,4-diamine

HRID 346691

Reaction equation

HRID 346691 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[C:15](Cl)[N:14]=[C:13]([Cl:18])[N:12]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[CH:19]1([NH2:26])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.O.[OH-].[Na+]>CC(C)=O.C(OCC)(=O)C>[Cl:18][C:13]1[N:12]=[C:11]([NH:10][C:4]2[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([Cl:1])[CH:3]=2)[N:16]=[C:15]([NH:26][CH:19]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[N:14]=1

Participants

7

Reactant 4

HCID 962WaterHCID 2899CycloheptylamineHCID 14798Sodium HydroxideHCID 21896921(3-Chloro-4-methoxy-phenyl)-(4,6-dichloro-[1,3,5]triazin-2-yl)-amine

Product 1

HCID 218970216-chloro-N-(3-chloro-4-methoxyphenyl)-N'-cycloheptyl-[1,3,5]triazine-2,4-diamineYield 70.5%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a sample of compound 101 (20.02 g, 65.6 mmol) in acetone (200 mL) was added cycloheptylamine (8.3 mL, 65.5 mmol) in acetone (55 mL) slowly by addition funnel at rt. Then water (66 mL) was added followed by aqueous sodium hydroxide (26.2 mL, 2.5 N, 65.5 mmol) by addition funnel. The reaction mixture was heated at reflux under a nitrogen atmosphere for approximately about 3 hours. The reaction was cooled, diluted with ethyl acetate, washed 1 time with water, and finally 1 time with brine. The organic layer was separated and dried over potassium carbonate/sodium sulfate. The organic layer was filtered and concentrated in vacuo. The product (24.13 g) was purified by flash column chromatography (silica gel, 1:4 ethyl acetate: hexanes). The fractions were combined and concentrated in vacuo to afford 133 as a pale yellow solid (17.66 g, 70.5%), mp 146° C.; HPLC: Inertsil ODS-3V C18, 40:10:50 [KH2PO4 (0.01M, pH 3.2): CH3OH: CH3CN], 264 nm, Rt 58.8 min, 99.9% purity); MS (ESI): m/z 382 (M+H, 100), 241 (2.8), 226 (8.4), 139 (43.5), 116 (6).

Workup

  1. additionslowly by addition funnel at rt
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux under a nitrogen atmosphere for approximately about 3 hours
  4. temperatureThe reaction was cooled
  5. washwashed 1 time with water, and finally 1 time with brine
  6. customThe organic layer was separated
  7. dry with materialdried over potassium carbonate/sodium sulfate
  8. filtrationThe organic layer was filtered
  9. concentrationconcentrated in vacuo
  10. customThe product (24.13 g) was purified by flash column chromatography (silica gel, 1:4 ethyl acetate: hexanes)
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fc2bf8fdb57642bd908f3ac8e167feee
Source dataset
uspto-grants-2007_02
Patent number
US07173032B2

Linked notes

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