Hydroxylamine HCl → HCID 136052386, compound

HRID 1889516Notes

Reaction equation

HRID 1889516 reaction equation
[Cl-].[OH:2][NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].F[C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1[C:17](=O)[CH2:18][N:19]1[C:24](=[O:25])[C:23]2[CH:26]=[C:27]([CH2:29][C:30]([F:33])([F:32])[F:31])[S:28][C:22]=2[N:21]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([C:41]3[C:42]([C:47]#[N:48])=[CH:43][CH:44]=[CH:45][CH:46]=3)=[CH:37][CH:36]=2)[C:20]1=[O:49].[N:51]12CCCN=C1CCCCC2>C(Cl)(Cl)Cl.C(Cl)Cl.CS(C)=O>[F:16][C:14]1[CH:15]=[CH:10][C:11]2[C:17]([CH2:18][N:19]3[C:24](=[O:25])[C:23]4[CH:26]=[C:27]([CH2:29][C:30]([F:32])([F:33])[F:31])[S:28][C:22]=4[N:21]([CH2:34][C:35]4[CH:36]=[CH:37][C:38]([C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=5[C:47]5[NH:51][C:4](=[O:7])[O:5][N:48]=5)=[CH:39][CH:40]=4)[C:20]3=[O:49])=[N:3][O:2][C:12]=2[CH:13]=1

Participants

8

Reactant 4

HCID 21645Hydroxylamine HClHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 516892Sodium BicarbonateHCID 593514994'-{[3-[2-(2,4-difluorophenyl)-2-oxoethyl]-2,4-dioxo-6-(2,2,2-trifluoroethyl)-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 136052386HCID 136052386, compoundYield 4%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 6212ChloroformSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (1.15 g), sodium hydrogencarbonate (1.66 g) and dimethyl sulfoxide (20 mL) was stirred at 40° C. for 30 min, 4′-{[3-[2-(2,4-difluorophenyl)-2-oxoethyl]-2,4-dioxo-6-(2,2,2-trifluoroethyl)-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile (0.98 g) was added, and the mixture was stirred at 90° C. for 16 hr. The reaction mixture was diluted with chloroform, washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue obtained by silica gel column chromatography was dissolved in methylene chloride (20 mL), N,N′-carbonyldiimidazole (0.3 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.25 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with chloroform, washed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as a colorless amorphous solid (0.04 g, 4%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 16 hr
  2. washwashed successively with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customThe residue obtained by silica gel column chromatography
  6. stirringthe mixture was stirred at room temperature for 2 hr
  7. washwashed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-cb54fcfcf14746738b5a163a50fc8156
Source dataset
uspto-grants-2013_08
Patent number
US08501750B2

Reaction notes

Loading…