Hydrochloric Acid → HCID 57329926, compound

HRID 336356Notes

Reaction equation

HRID 336356 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:11][C:12]1[CH:13]=[C:14]([CH:34]=[CH:35][CH:36]=1)[CH2:15][CH:16]1[CH2:20][CH2:19][CH2:18][N:17]1[C:21]([C:23]1[C:32](Cl)=[N:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:24]=1)=[O:22].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2[N:56](C)C)CCCCC1.Cl.[OH-].[Na+]>O1CCOCC1.[Cl-].[Na+].O.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[NH2:56][C:32]1[C:23]([C:21]([N:17]2[CH2:18][CH2:19][CH2:20][CH:16]2[CH2:15][C:14]2[CH:34]=[CH:35][CH:36]=[C:12]([Cl:11])[CH:13]=2)=[O:22])=[N:24][C:25]2[C:30]([N:31]=1)=[CH:29][CH:28]=[CH:27][CH:26]=2

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2733832Lithium HexamethyldisilazideHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 57329925HCID 57329925, compound

Product 1

HCID 57329926HCID 57329926, compound

Reagents, catalysts & solvents 3

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Lithium bis(trimethylsilyl)amide (1.3 mL, 1.34 mmol, 1.0 M in THF) was added dropwise to a degassed mixture of (2-(3-chlorobenzyl)pyrrolidin-1-yl)(3-chloroquinoxalin-2-yl)methanone (235 mg, 0.61 mmol), tris(dibenzylideneacetone) dipalladium(0) (28 mg, 5 mol %) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (12 mg, 5 mol %) in anhydrous 1,4-dioxane (5.0 mL) at room temperature under nitrogen, after which the mixture was heated to reflux to stir for 16 h. The cooled mixture was treated with 1 N HCl (2 mL), stirred for 30 min and the adjusted to pH 10 with 2 N sodium hydroxide solution and diluted with brine (100 mL). The mixture was extracted with ethyl acetate (2×150 mL) and the combined organic extracts were washed with brine (100 mL), dried over magnesium sulfate and filtered. The filtrate solvents were removed under reduced pressure and the residue was purified by flash column chromatography on silica gel, eluting with hexanes/ethyl acetate (1:1), to provide (3-aminoquinoxalin-2-yl)(2-(3-chlorobenzyl)pyrrolidin-1-yl)methanone as a brown oil: 1H NMR (400 MHz, CDCl3, ˜2:1 mixture of rotamers) δ 7.88 (d, J=9.5 Hz, 1H, rotamers A and B), 7.67-7.63 (m, 1H, rotamers A and B), 7.49-7.11 (m, 1H, rotamers A and B), 7.34 (s, 1H, rotamer A), 7.28-7.19 (m, 1H, rotamers A and B and 3H, rotamer A), 7.09 (d, J=8.9 Hz, rotamer B), 7.00 (t, J=7.8 Hz, rotamer B), 6.88 (s, 1H, rotamer B), 6.73 (d, J=7.8 Hz, 1H, rotamer B), 6.19 (s, 2H, NH2, rotamer A), 6.08 (s, 2H, NH2, rotamer B), 5.22-5.15 (m, 1H, rotamer B), 4.61-4.54 (m, 1H, rotamer A), 3.96-3.89 (m, 2H, rotamer B), 3.84-3.73 (m, 2H, rotamer A), 3.37 (dd, J=3.3. 12.8 Hz, 1H, rotamer A), 2.95 (dd, J=5.0, 13.4 Hz, 1H, rotamer B), 2.83-2.73 (m, 1H, rotamer A), 2.59-2.53 (m, 1H, rotamer B), 2.07-1.75 (m, 4H, rotamers A and B) ppm; ESI MS m/z 367 [M+H]+.

Workup

  1. temperatureafter which the mixture was heated
  2. temperatureto reflux
  3. stirringstirred for 30 min
  4. extractionThe mixture was extracted with ethyl acetate (2×150 mL)
  5. washthe combined organic extracts were washed with brine (100 mL)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customThe filtrate solvents were removed under reduced pressure
  9. customthe residue was purified by flash column chromatography on silica gel
  10. washeluting with hexanes/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-d5fafef704814a1da7e9036e0f2138b3
Source dataset
uspto-grants-2014_11
Patent number
US08889683B2

Reaction notes

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