p-Toluenesulfonic acid → p-Toluenesulfonate

HRID 530377Notes

Reaction equation

HRID 530377 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH:9]2[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]2)[CH:5]=[CH:4][N:3]=1.[CH3:22][C:23]1[CH:24]=[C:25]([NH2:35])[CH:26]=[C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:28]=1.[CH3:36][C:37]1[CH:38]=[CH:39][C:40]([S:43]([OH:46])(=[O:45])=[O:44])=[CH:41][CH:42]=1>O1CCOCC1>[CH3:22][C:23]1[CH:24]=[C:25]([NH:35][C:2]2[N:7]=[C:6]([O:8][CH:9]3[CH2:10][CH2:11][NH:12][CH2:13][CH2:14]3)[CH:5]=[CH:4][N:3]=2)[CH:26]=[C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:28]=1.[S:43]([C:40]1[CH:41]=[CH:42][C:37]([CH3:36])=[CH:38][CH:39]=1)([O-:46])(=[O:45])=[O:44]

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 11819709[1,1'-Biphenyl]-3-amine, 5-methyl-HCID 71629906tert-Butyl 4-((2-chloropyrimidin-4-yl)oxy)piperidine-1-carboxylate

Product 2

HCID 85570p-ToluenesulfonateHCID 90042042N-(5-methylbiphenyl-3-yl)-4-(piperidin-4-yloxy)pyrimidin-2-amine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of tert-butyl 4-[(2-chloropyrimidin-4-yl)oxy]piperidine-1-carboxylate (62.8 mg, 0.2 mmol) and 5-methylbiphenyl-3-amine (36.6 mg, 0.2 mmol) in 0.1 M 1:1 TsOH:dioxane (2.0 mL) was heated to 100° C. overnight. Upon cooling to room temperature, the reaction mixture was concentrated in vacuo. The resulting light yellow solid was triturated in 1:1 dichloromethane:diethyl ether (10 mL). The solid was removed by filtration then dried under vacuum to provide N-(5-methylbiphenyl-3-yl)-4-(piperidin-4-yloxy)pyrimidin-2-amine as a tosylate salt as a light yellow solid. MS ESI calc'd. for C22H25N4O [M+H]+ 361, found 362. 1H NMR (400 MHz, DMSO-d6): δ 10.17 (s, 1H); 8.68 (s, 2H); 8.29 (d, J=6.4 Hz, 1H); 7.76 (s, 1H); 7.63 (d, J=7.9 Hz, 1H); 7.61-7.26 (m, 1H); 7.21 (s, 1H); 7.12 (d, J=8.1 Hz, 2H); 6.43 (d, J=6.4 Hz, 1H); 5.26 (s, 1H); 3.19 (s, 2H); 2.97 (s, 2H); 2.29 (s, 2H); 2.14 (s, 2H); 1.95 (s, 3H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customThe resulting light yellow solid was triturated in 1:1 dichloromethane
  3. customThe solid was removed by filtration
  4. customthen dried under vacuum

Sources & evidence

ORD record
ord-ce8ede3e9f034e62930661a96f2357d9
Source dataset
uspto-grants-2016_05
Patent number
US09353066B2

Reaction notes

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