p-Toluenesulfonic acid monohydrate → HCID 59442746, compound

HRID 1746159Notes

Reaction equation

HRID 1746159 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:14][C:13]([CH3:16])([CH3:15])[NH:12][C:11]([CH3:18])([CH3:17])[CH2:10]2)[C:5]([F:19])=[CH:4][N:3]=1.[CH:20]1([C:23]2[CH:24]=[C:25]([NH2:35])[CH:26]=[C:27]([C:29]3[N:33]([CH3:34])[N:32]=[N:31][N:30]=3)[CH:28]=2)[CH2:22][CH2:21]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)(C)C>[CH:20]1([C:23]2[CH:24]=[C:25]([NH:35][C:2]3[N:7]=[C:6]([NH:8][CH:9]4[CH2:14][C:13]([CH3:16])([CH3:15])[NH:12][C:11]([CH3:18])([CH3:17])[CH2:10]4)[C:5]([F:19])=[CH:4][N:3]=3)[CH:26]=[C:27]([C:29]3[N:33]([CH3:34])[N:32]=[N:31][N:30]=3)[CH:28]=2)[CH2:22][CH2:21]1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 59442717HCID 59442717, compoundHCID 59442725HCID 59442725, compound

Product 1

HCID 59442746HCID 59442746, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

2-Chloro-5-fluoro-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidin-4-amine (90 mg, 0.31 mmol) was treated with 3-cyclopropyl-5-(1-methyl-1H-tetrazol-5-yl)benzenamine (80 mg, 0.37 mmol) and p-toluenesulfonic acid monohydrate (48 mg, 0.25 mmol) in isopropanol (5 mL) and heated at reflux, in a loosely capped vial, overnight. The solvent evaporated, over the course of the reaction. 2-Chloro-5-fluoro-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidin-4-amine remained in the reaction mixture. An additional equivalent of 3-cyclopropyl-5-(1-methyl-1H-tetrazol-5-yl)benzenamine was added, along with more isopropanol. The reaction was allowed to heat at reflux for an additional 8 hours. This process was repeated until the 2-chloro-5-fluoro-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidin-4-amine was consumed, 4 days later. The resulting residue was purified by column chromatography, on silica gel, eluting with methanol:methylene chloride (1:99) followed by 2M ammonia in methanol:methylene chloride (2:98), to yield N2-(3-cyclopropyl-5-(1-methyl-1H-tetrazol-5-yl)phenyl)-5-fluoro-N4-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine (60 mg, 42% yield) as an off-white solid.

Workup

  1. temperatureheated
  2. temperatureat reflux
  3. customovernight
  4. customThe solvent evaporated, over the course of the reaction
  5. additionAn additional equivalent of 3-cyclopropyl-5-(1-methyl-1H-tetrazol-5-yl)benzenamine was added, along with more isopropanol
  6. temperatureto heat
  7. temperatureat reflux for an additional 8 hours
  8. customwas consumed, 4 days later
  9. customThe resulting residue was purified by column chromatography, on silica gel
  10. washeluting with methanol:methylene chloride (1:99)

Sources & evidence

ORD record
ord-c5b2834bd6824512a2927dcd450e260a
Source dataset
uspto-grants-2015_10
Patent number
US09149475B2

Reaction notes

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