p-Toluenesulfonic acid monohydrate → HCID 56644519, compound

HRID 2370945Notes

Reaction equation

HRID 2370945 reaction equation
[CH3:1][C:2]1([CH3:20])[CH2:7][CH:6]([NH:8][C:9]2[C:14]([C:15]#[N:16])=[CH:13][N:12]=[C:11](Cl)[N:10]=2)[CH2:5][C:4]([CH3:19])([CH3:18])[NH:3]1.[CH:21]1([C:24]2[C:29]([N:30]3[CH:34]=[N:33][N:32]=[N:31]3)=[CH:28][C:27]([NH2:35])=[C:26]([F:36])[CH:25]=2)[CH2:23][CH2:22]1.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>[CH3:1][C:2]1([CH3:20])[CH2:7][CH:6]([NH:8][C:9]2[C:14]([C:15]#[N:16])=[CH:13][N:12]=[C:11]([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]4[CH2:22][CH2:23]4)=[CH:25][C:26]=3[F:36])[N:10]=2)[CH2:5][C:4]([CH3:19])([CH3:18])[NH:3]1

Participants

6

Reactant 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 58065786HCID 58065786, compoundHCID 66683869HCID 66683869, compoundHCID 86661498HCID 86661498, compound

Product 1

HCID 56644519HCID 56644519, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-(2,2,6,6-tetramethylpiperidin-4-ylamino)-2-chloropyrimidine-5-carbonitrile (112 mg, 0.380 mmol, 1 equiv), 4-cyclopropyl-2-fluoro-5-(1H-tetrazol-1-yl)benzenamine (100 mg, 0.456 mmol, 1.2 equiv), and para-toluenesulfonic acid monohydrate (58 mg, 0.304 mmol, 0.8 equiv) in IPA (4 mL) were heated to 80° C. overnight. LCMS indicated desired product plus approximately 18% 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 (88 mg, 49%) as a solid.

Sources & evidence

ORD record
ord-62b702f8f7ed42f9aaa06fa706462ddf
Source dataset
uspto-grants-2014_04
Patent number
US08710223B2

Reaction notes

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