Diisopropylethylamine → N-Azepan-1-yl-N'-(3-chloro-4-methoxy-phenyl)-N''-(1-methyl-piperidin-4-yl)-[1,3,5]triazine-2,4,6-triamine

HRID 916105Notes

Reaction equation

HRID 916105 reaction equation
[N:1]1([NH:8][C:9]2[N:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([Cl:24])[CH:17]=3)[N:12]=[C:11](Cl)[N:10]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:26][N:27]1[CH2:32][CH2:31][CH:30]([NH:33]C)[CH2:29][CH2:28]1.CCN(C(C)C)C(C)C>C1COCC1.C(#N)C>[OH-:22].[NH4+:1].[N:1]1([NH:8][C:9]2[N:14]=[C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([Cl:24])[CH:17]=3)[N:12]=[C:11]([NH:33][CH:30]3[CH2:31][CH2:32][N:27]([CH3:26])[CH2:28][CH2:29]3)[N:10]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 5663231-Methyl-4-(methylamino)piperidineHCID 21896980N-Azepan-1-yl-6-chloro-N'-(3-chloro-4-methoxy-phenyl)-[1,3,5]triazine-2,4-diamine

Product 2

HCID 14923Ammonium HydroxideHCID 21897034N-Azepan-1-yl-N'-(3-chloro-4-methoxy-phenyl)-N''-(1-methyl-piperidin-4-yl)-[1,3,5]triazine-2,4,6-triamineYield 56.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To 152 (0.2007 g, 0.5 mmol) dissolved in THF (10 mL) was added a solution of N-methyl-4(methylamino)piperidine (0.07 mL, 0.5 mmol) in THF (1 mL) followed by the addition of DIEA (1.0 mL, 0.55 mmol) in acetonitrile (1 mL). The reaction mixture was allowed to stir at reflux overnight under nitrogen. The reaction mixture was extracted 3 times with dichloromethane; the combined organic layers were washed with brine and dried over potassium carbonate. The sample was concentrated on a rotary evaporator and the resulting oil was dried overnight under vacuum. Column chromatography (90:9:1 dichloromethane:methanol:conc. ammonium hydroxide) yielded a light yellow solid 154 (65 mg, 27%), mp 100° C.; TLC (silica gel, 90:9:1 CH2Cl2:CH3OH, conc. NH4OH), Rf 0.36; MS (ESI): m/z 475 (M+H, 23.2), 378 (11.6), 258 (68.9), 239 (52.2), 238 (100).

Workup

  1. temperatureat reflux overnight under nitrogen
  2. extractionThe reaction mixture was extracted 3 times with dichloromethane
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over potassium carbonate
  5. concentrationThe sample was concentrated on a rotary evaporator
  6. customthe resulting oil was dried overnight under vacuum

Sources & evidence

ORD record
ord-7f812dd939a94283b2cec3a67196849e
Source dataset
uspto-grants-2007_09
Patent number
US07268134B2

Reaction notes

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