Hydrochloric Acid → HCID 131719124, compound

HRID 2399822Notes

Reaction equation

HRID 2399822 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][CH:5]([C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:9]=1C(C)C)[C:6]#[N:7].[CH2:18](CN)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(N([CH:33]([CH3:35])[CH3:34])CC)(C)C.Cl.[CH3:37][N:38](C)C=O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.ClCCl>[ClH:1].[F:14][C:11]1[CH:10]=[CH:9][C:8]([C:5]([CH:33]([CH3:35])[CH3:34])([CH2:4][CH2:3][CH2:2][N:38]([CH3:37])[CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:6]#[N:7])=[CH:13][CH:12]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 1001PhenethylamineHCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 19384667HCID 19384667, compound

Product 1

HCID 131719124HCID 131719124, compound

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
57 °C

Procedure

The product from Example 2, Step (b) (2.61 g, 10.3 mmol) was diluted with dimethylformamide (6 mL). N-benzylmethylamine (1.42 mL, 11 mmol), diisopropylethylamine (1.91 mL, 11 mmol) and tetrabutylammoniumbromide (300 mg) were added and the mixture was stirred at 57° C. overnight, then at 77° C. for an additional 24 hours. The mixture was diluted with water (10 ml) and extracted with ethylacetate (100 mL, then 2×10 mL). The combined organic layers were dried over MgSO4, filtered through silica, and concentrated. Chromatography in silica gel afforded the free base, which was converted to the hydrochloride salt using hydrogen chloride gas in dichloromethane. The salt was recrystallized from a mixture of dichloromethane, methyl acetate and hexane, and characterized by NMR as follows: Analysis calcd. for C22H28ClFN2 : C, 70.48; H, 7.53; N, 7.47; Found: C, 70.09; H, 7.52; N, 7.33; 13CNMR free base (CDCl3, 100 MHz, partial): 62.2, 56.5, 53.1, 42.1, 37.9, 35.5, 23.4, 18.8, 18.6.

Workup

  1. waitat 77° C. for an additional 24 hours
  2. extractionextracted with ethylacetate (100 mL
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered through silica
  5. concentrationconcentrated
  6. customChromatography in silica gel afforded the free base, which
  7. customThe salt was recrystallized from a mixture of dichloromethane, methyl acetate and hexane

Sources & evidence

ORD record
ord-45acdceda85e43719cf1b5ded0f5a336
Source dataset
uspto-grants-1995_09
Patent number
US05451604

Reaction notes

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