Hydrochloric Acid → HCID 53373213, compound

HRID 515811Notes

Reaction equation

HRID 515811 reaction equation
[C:1](Cl)(Cl)=[S:2].[CH3:5][C:6]1[O:10][C:9]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]3([C:22]#[N:23])[CH2:21][CH2:20][CH2:19]3)=[CH:13][CH:12]=2)=[CH:8][CH:7]=1.N[C:25]1[CH:26]=[C:27]([CH3:33])[C:28]([C:31]#[N:32])=[N:29][CH:30]=1.Cl.CC(N(C)C)=[O:37]>O.CO>[CH3:33][C:27]1[C:28]([C:31]#[N:32])=[N:29][CH:30]=[C:25]([N:23]2[C:22](=[O:37])[C:18]3([CH2:21][CH2:20][CH2:19]3)[N:17]([C:14]3[CH:15]=[CH:16][C:11]([C:9]4[O:10][C:6]([CH3:5])=[CH:7][CH:8]=4)=[CH:12][CH:13]=3)[C:1]2=[S:2])[CH:26]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10040ThiophosgeneHCID 31374DimethylacetamideHCID 218645665-Amino-3-methylpyridine-2-carbonitrile2×HCID 67373505HCID 67373505, compound2×

Product 1

HCID 53373213HCID 53373213, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

Thiophosgene (0.1 mL) was added dropwise to a solution of 1-((4-(5-methylfuran-2-yl)phenyl)amino)cyclobutanecarbonitrile (Intermediate 106, 280 mg, 1.11 mmol) and 5-amino-3-methylpicolinonitrile (Intermediate 2, 177 mg, 1.33 mmol) in DMA (20 mL). The resulting mixture was stirred at 60° C. overnight. MeOH (16 mL) and HCl (2M, 8 mL) were added and the mixture was refluxed for 2 h then cooled to room temperature. The reaction mixture was poured into water (200 mL) and extracted with EtOAc. The organic layer was washed with brine, dried over Sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel (1:3 EtOAc/petroleum ether), to afford 140 mg of 3-methyl-5-(5-(4-(5-methylfuran-2-yl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)picolinonitrile. 1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 1H), 8.16 (s, 1H), 7.86 (d, 2H), 7.46 (d, 2H), 6.98 (d, 1H), 6.28 (d, 1H), 2.63 (m, 2H), 2.60 (s, 3H), 2.51-2.43 (m, 2H), 2.38 (s, 3H), 1.97 (m, 1H), 1.57 (m, 1H). LCMS [M+1]+ 429.1.

Workup

  1. temperaturethe mixture was refluxed for 2 h
  2. temperaturethen cooled to room temperature
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography on silica gel (1:3 EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-f4b932e25d2d444fa6ebb48326a2584e
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

Loading…