Benzenesulfonic Acid → Benzenesulfonic Acid

HRID 1754442Notes

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-fc70ee92fc2c4330ae6d71794b596ede
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169249B2

Reaction notes

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