p-Toluenesulfonic acid → HCID 59442740, compound

HRID 388243Notes

Reaction equation

HRID 388243 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:28]=[CH:27][C:26]([NH2:29])=[CH:25][C:24]=2[N:30]2[CH:34]=[N:33][N:32]=[N:31]2)[CH2:22][CH2:21]1.S(O)(C1C=CC(C)=CC=1)(=O)=O>CC(O)C>[CH:20]1([C:23]2[CH:28]=[CH:27][C:26]([NH:29][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:25][C:24]=2[N:30]2[CH:34]=[N:33][N:32]=[N:31]2)[CH2:22][CH2:21]1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 59442725HCID 59442725, compound2×HCID 59442739HCID 59442739, compound

Product 1

HCID 59442740HCID 59442740, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
100 °C

Procedure

In a 100 mL round bottom flask to a solution of 2-chloro-5-fluoro-N-(2,2,6,6,-tetramethylpiperidin-4-yl)pyrimidin-4-amine (Compound 15; 0.18 g, 0.63 mmol) in 10 mL iPrOH, 4-cyclopropyl-3-(1H-tetrazol-1-yl)benzeneamine (0.18 g, 0.88 mmol) and TosOH (0.095 g, 0.50 mmol) were added. The reaction mixture was heated at 100° C. for 3 hours. LCMS analysis indicated the complete consumption of the mono-SNAr product and appearance of Compound III-118. The reaction mixture was then cooled to room temperature and volatiles were removed under reduced pressure. The crude reaction mixture was purified by column chromatography using DCM/2 M NH3 in MeOH to get tan solid that was further purified by tituration using DCM/hexanes.

Workup

  1. customthe complete consumption of the mono-SNAr product and appearance of Compound III-118
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. customvolatiles were removed under reduced pressure
  4. customThe crude reaction mixture
  5. customwas purified by column chromatography
  6. customto get tan solid
  7. customthat was further purified by tituration

Sources & evidence

ORD record
ord-0cdee18d2a0144be8ba16d4fb4ebd513
Source dataset
uspto-grants-2013_02
Patent number
US08377924B2

Reaction notes

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