p-Toluenesulfonic acid monohydrate → Ammonia methanol

HRID 2370967Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:14][C:13]([CH3:16])([CH3:15])[N:12]([CH3:17])[C:11]([CH3:19])([CH3:18])[CH2:10]2)[C:5]([C:20]#[N:21])=[CH:4][N:3]=1.[CH:22]1([C:25]2[C:30]([N:31]3[CH:35]=[N:34][N:33]=[N:32]3)=[CH:29][C:28]([NH2:36])=[C:27]([F:37])[CH:26]=2)[CH2:24][CH2:23]1.[OH2:38].C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(O)C>[NH3:3].[CH3:2][OH:38].[CH3:17][N:12]1[C:13]([CH3:16])([CH3:15])[CH2:14][CH:9]([NH:8][C:6]2[C:5]([C:20]#[N:21])=[CH:4][N:3]=[C:2]([NH:36][C:28]3[CH:29]=[C:30]([N:31]4[CH:35]=[N:34][N:33]=[N:32]4)[C:25]([CH:22]4[CH2:23][CH2:24]4)=[CH:26][C:27]=3[F:37])[N:7]=2)[CH2:10][C:11]1([CH3:19])[CH3:18]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 2-chloro-5-cyano-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidin-4-amine (0.205 g, 0.66 mmol, 1 equiv), 4-cyclopropyl-2-fluoro-5-(1H-tetrazol-1-yl)benzenamine (0.160 g, 0.730 mmol, 1.1 equiv), and para-toluenesulfonic acid monohydrate (0.100 g, 0.530 mmol, 0.8 equiv) in IPA (25 mL) were heated to 100° C. overnight. 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 2% 2M NH3/MeOH increments) to provide the desired product which was recrystallized with DCM/Hexanes to give the title compound (0.170 mg, 52%) as a solid.

Workup

temperatureAfter cooling to ambient temperature
customthe crude mixture was quenched with 2M NH3/MeOH
concentrationby concentrating to dryness
customThe crude product was purified by flash chromatography
washeluted with DCM

Sources & evidence

ORD record: ord-c4e46727171e446f988b7eb39256efa1
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08710223B2

Reaction notes

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