HCID 86683486, compound → HCID 53373088, compound

HRID 515824Notes

Reaction equation

HRID 515824 reaction equation
[C:1]([C:3]1[N:8]=[CH:7][C:6]([N:9]2[C:16](=[O:17])[C:12]3([CH2:15][CH2:14][CH2:13]3)[N:11]([C:18]3[CH:37]=[CH:36][C:21]([O:22][CH:23]4[CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24]4)=[CH:20][CH:19]=3)[C:10]2=[S:38])=[CH:5][C:4]=1[CH3:39])#[N:2]>Cl.CO>[CH3:39][C:4]1[C:3]([C:1]#[N:2])=[N:8][CH:7]=[C:6]([N:9]2[C:16](=[O:17])[C:12]3([CH2:13][CH2:14][CH2:15]3)[N:11]([C:18]3[CH:19]=[CH:20][C:21]([O:22][CH:23]4[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]4)=[CH:36][CH:37]=3)[C:10]2=[S:38])[CH:5]=1

Participants

3

Reactant 1

HCID 86683486HCID 86683486, compound2×

Product 1

HCID 53373088HCID 53373088, compoundYield 93.4%

Reagents, catalysts & solvents 1

HCID 21893726Hydrochloride methanolSolvent

Procedure

Tert-butyl 4-(4-(7-(6-cyano-5-methylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)phenoxy)piperidine-1-carboxylate (prepared by reaction of 5-(5-(4-hydroxyphenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-methylpicolinonitrile (Compound 77) with tert-butyl 4-hydroxypiperidine-1-carboxylate, according to Example 16, 300 mg, 0.55 mmol) was stirred in 2M HCl/methanol (1.5 mL) at room temperature overnight. The mixture was concentrated and purified by column chromatography, eluting with 10% MeOH/DCM to provide 230 mg of 3-methyl-5-(8-oxo-5-(4-(piperidin-4-yloxy)phenyl)-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)picolinonitrile as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.72 (d, 1H), 8.14 (d, 1H), 7.30 (d, 2H), 7.13 (d, 2H), 4.53-4.42 (m, 1H), 3.94-3.86 (m, 1H), 3.02-2.83 (m, 3H), 2.66-2.50 (m, 5H), 2.49-2.33 (m, 3H), 2.11-1.80 (m, 3H), 1.60-1.33 (m, 3H). LCMS [M+1]+ 448.1.

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified by column chromatography
  3. washeluting with 10% MeOH/DCM

Sources & evidence

ORD record
ord-9953897d25354a5b8ce5f40aef90944a
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

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