p-Toluenesulfonic acid monohydrate → HCID 56644517, compound

HRID 710219Notes

Reaction equation

HRID 710219 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]([C:19]#[N:20])=[CH:4][N:3]=1.[CH:21]([C:24]1[C:29]([N:30]2[CH:34]=[N:33][N:32]=[N:31]2)=[CH:28][C:27]([NH2:35])=[C:26]([F:36])[CH:25]=1)([CH3:23])[CH3:22].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.FC1C(NC2CC(C)(C)NC(C)(C)C2)=NC(OC(C)C)=NC=1>CC(O)C>[CH3:15][C:13]1([CH3:16])[CH2:14][CH:9]([NH:8][C:6]2[C:5]([C:19]#[N:20])=[CH:4][N:3]=[C:2]([NH:35][C:27]3[CH:28]=[C:29]([N:30]4[CH:34]=[N:33][N:32]=[N:31]4)[C:24]([CH:21]([CH3:22])[CH3:23])=[CH:25][C:26]=3[F:36])[N:7]=2)[CH2:10][C:11]([CH3:18])([CH3:17])[NH:12]1

Participants

6

Reactant 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 58065811HCID 58065811, compoundHCID 66683869HCID 66683869, compoundHCID 86661498HCID 86661498, compound

Product 1

HCID 56644517HCID 56644517, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-chloro-5-cyano-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidin-4-amine (0.05 g, 0.17 mmol, 1 equiv), 4-isopropyl-2-fluoro-5-(1H-tetrazol-1-yl)benzenamine (0.045 g, 0.204 mmol, 1.2 equiv), and para-toluenesulfonic acid monohydrate (0.025 g, 0.136 mmol, 0.8 equiv) in IPA (5 mL) were heated to 80° C. overnight. LCMS indicated desired product plus approximately 10% of 5-fluoro-2-isopropoxy-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidin-4-amine byproduct. After cooling to ambient temperature, the crude mixture was quenched with 2M NH3/MeOH followed by concentrating to dryness and repeating once. The crude product was purified by flash chromatography and eluted with DCM:2M NH3/MeOH (100:0 to 95:5 using 1% 2M NH3/MeOH increments) to provide the desired product which was recrystallized with DCM/IPA to give the title compound (45 mg, 55%) as a solid.

Sources & evidence

ORD record
ord-bb7c40d75824441cb6b719d71a50e989
Source dataset
uspto-grants-2015_11
Patent number
US09181222B2

Reaction notes

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