Water → HCID 53373220, compound

HRID 515823Notes

Reaction equation

HRID 515823 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:15](=[S:16])[N:14]([C:17]3[CH:18]=[C:19]([C:25]([F:28])([F:27])[F:26])[C:20]([C:23]#[N:24])=[N:21][CH:22]=3)[C:13](=[O:29])[C:9]32[CH2:12][CH2:11][CH2:10]3)=[CH:4][CH:3]=1.Cl[C:31]1[N:36]=[CH:35][CH:34]=[CH:33][N:32]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>C1COCC1>[O:29]=[C:13]1[C:9]2([CH2:12][CH2:11][CH2:10]2)[N:8]([C:5]2[CH:6]=[CH:7][C:2]([O:1][C:31]3[N:36]=[CH:35][CH:34]=[CH:33][N:32]=3)=[CH:3][CH:4]=2)[C:15](=[S:16])[N:14]1[C:17]1[CH:18]=[C:19]([C:25]([F:28])([F:27])[F:26])[C:20]([C:23]#[N:24])=[N:21][CH:22]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 744042-ChloropyrimidineHCID 86683483HCID 86683483, compound2×

Product 1

HCID 53373220HCID 53373220, compoundYield 50.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 5-(5-(4-hydroxyphenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile (Compound 63, 50 mg, 0.12 mmol), 2-chloropyrimidine (17 mg, 0.15 mmol), and cesium carbonate (60 mg, 0.18 mmol) in anhydrous THF (1.2 mL) was heated at reflux overnight. The reaction mixture was cooled to room temperature and water was added. The aqueous was extracted with EtOAc (3×), the organics combined and washed with brine, dried (MgSO4) and concentrated. Purification by column chromatography on silica gel eluting with 0 to 60% EtOAc/hexanes provided 30 mg of 5-(8-oxo-5-(4-(pyrimidin-2-yloxy)phenyl)-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ 9.24 (d, 1H), 8.78 (d, 1H), 8.73 (d, 2H), 7.48 (dd, 4H), 7.35 (t, 1H), 2.72-2.61 (m, 2H), 2.54-2.42 (m, 2H), 2.10-1.93 (m, 1H), 1.69-1.52 (m, 1H). LCMS [M+1]+ 497.8.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. extractionThe aqueous was extracted with EtOAc (3×)
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customPurification by column chromatography on silica gel eluting with 0 to 60% EtOAc/hexanes

Sources & evidence

ORD record
ord-25dae6ff65474a3098bd70b3d3a2d6a3
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

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