Benzenesulfonic Acid → Benzenesulfonic Acid

HRID 633385Notes

Reaction equation

[NH2:1][C:2]1[C:3]([F:16])=[CH:4][C:5]([OH:15])=[C:6]([N:8]2[C:12](=[O:13])[N:11]([CH3:14])[N:10]=[N:9]2)[CH:7]=1.Cl[C:18]1[N:23]=[C:22]([NH:24][C@@H:25]2[CH2:33][C@H:32]3[N:28]([CH2:29][CH2:30][CH2:31]3)[C:27]([CH3:35])([CH3:34])[CH2:26]2)[C:21]([C:36]#[N:37])=[CH:20][N:19]=1.[C:38]1([S:44]([OH:47])(=[O:46])=[O:45])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>CC(O)C>[CH3:34][C:27]1([CH3:35])[CH2:26][C@H:25]([NH:24][C:22]2[C:21]([C:36]#[N:37])=[CH:20][N:19]=[C:18]([NH:1][C:2]3[C:3]([F:16])=[CH:4][C:5]([OH:15])=[C:6]([N:8]4[C:12](=[O:13])[N:11]([CH3:14])[N:10]=[N:9]4)[CH:7]=3)[N:23]=2)[CH2:33][C@H:32]2[N:28]1[CH2:29][CH2:30][CH2:31]2.[C:38]1([S:44]([OH:47])(=[O:46])=[O:45])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 1-(5-amino-4-fluoro-2-hydroxyphenyl)-4-methyl-1H-tetrazol-5(4H)-one (210 mg), (7R,8aS)-N-(2-chloro-5-cyanopyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine (220 mg), and benzenesulfonic acid (200 mg) in IPA (2 mL) were heated to 80° C. for overnight. After cooling to ambient temperature, the crude mixture was concentrated to dryness. The crude product was absorbed onto silica gel and purified by CombiFlash chromatography (2N NH3 in MeOH/CH2Cl2=0-30%) to give compound 1-(5-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-5-cyanopyrimidin-2-ylamino)-4-fluoro-2-hydroxyphenyl)-4-methyl-1H-tetrazol-5(4H)-one (540 mg with some benzenesulfonic acid).

Workup

temperatureAfter cooling to ambient temperature
concentrationthe crude mixture was concentrated to dryness
customThe crude product was absorbed onto silica gel
custompurified by CombiFlash chromatography (2N NH3 in MeOH/CH2Cl2=0-30%)

Sources & evidence

ORD record: ord-acba6897409648e89581a4e866d2068a
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321763B2

Reaction notes

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