Ethyl orthoformate → HCID 86683477, compound

HRID 515816Notes

Reaction equation

HRID 515816 reaction equation
[NH2:1][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][C:3]=1[OH:30].[CH2:31](OC(OCC)OCC)C>CN(C=O)C.O>[O:30]1[C:3]2[CH:4]=[C:5]([N:8]3[C:15](=[S:16])[N:14]([C:17]4[CH:18]=[C:19]([C:25]([F:28])([F:27])[F:26])[C:20]([C:23]#[N:24])=[N:21][CH:22]=4)[C:13](=[O:29])[C:9]43[CH2:12][CH2:11][CH2:10]4)[CH:6]=[CH:7][C:2]=2[N:1]=[CH:31]1

Participants

5

Reactant 2

HCID 31214Ethyl orthoformateHCID 86683478HCID 86683478, compound

Product 1

HCID 86683477HCID 86683477, compoundYield 37.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-(5-(4-amino-3-hydroxyphenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile (60 mg, 0.14 mmol) and triethylorthoformate (0.050 mL, 0.28 mmol) in anhydrous DMF (1 mL) was heated at 100° C., 1 h. The mixture was diluted with water, extracted with EtOAc (3×), the organics combined and washed with water (2×), brine, dried (MgSO4) and concentrated. Purification by column chromatography, eluting with 30% EtOAc/hexanes provided 23 mg of 5-(5-(benzo[d]oxazol-6-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile as a pale yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 9.24 (d, 1H), 8.95 (s, 1H), 8.78 (d, 1H), 8.05 (d, 1H), 7.94 (d, 1H), 7.45 (dd, 1H), 2.74-2.61 (m, 2H), 2.59-2.47 (m, 2H), 2.03-1.90 (m, 1H), 1.61-1.48 (m, 1H). LCMS [M+1]+ 444.0.

Workup

  1. extractionextracted with EtOAc (3×)
  2. washwashed with water (2×), brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customPurification by column chromatography
  6. washeluting with 30% EtOAc/hexanes

Sources & evidence

ORD record
ord-0a11d3819bee44b6934f3b924b3dc399
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

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