Dimethylformamide → HCID 178520782, compound

HRID 2383432Notes

Reaction equation

HRID 2383432 reaction equation
[Cl-].[C:2]1([C:8]2[C:20]3[C:19]4[CH2:18][CH2:17][NH2+:16][CH2:15][C:14]=4[CH:13]=[N:12][C:11]=3[NH:10][N:9]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:30][CH:31]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:32](Cl)=[O:33].CN(C)C=O>ClCCl.O>[Cl:30][CH:31]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:32]([N:16]1[CH2:15][C:14]2[CH:13]=[N:12][C:11]3[NH:10][N:9]=[C:8]([C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[C:20]=3[C:19]=2[CH2:18][CH2:17]1)=[O:33]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 102902Chloro(phenyl)acetyl chloride2×HCID 1784779931-phenyl-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-7-ium chloride

Product 1

HCID 178520782HCID 178520782, compoundYield 52.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 1-phenyl-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-7-ium chloride (0.184 g, 0.57 mmol) in dichloromethane (15 mL) was added Hunig's Base (0.45 mL, 2.56 mmol). The mixture was vortexed to ensure dissolution of the reagents followed by the addition of 2-chloro-2-phenylacetyl chloride (0.103 mL, 0.64 mmol). Dimethylformamide (6 mL) and 2-chloro-2-phenylacetyl chloride (15 μL, 0.093 mmol)) was then added and the reaction stirred for another 30 minute at room temperature. On completion of the reaction, water (30 mL) were added and the aqueous layer extracted with EtOAc (50 mL). The organic layer was separated, washed with brine (2×10 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to give the crude product. The crude product was purified using flash column chromatography (SiO2, gradient from 60% EtOAc in hexane to 66% EtOAc in hexane) to give the pure desired product, 2-chloro-2-phenyl-1-(1-phenyl-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-7(6H)-yl)ethanone as an off-white solid (0.120 g, 52%). 1H NMR (400 MHz, DMSO-d6) δ 13.72 (s, 1H), 8.40/8.25 (s, 1H, rotamers), 7.47 (m, 10H), 6.48 (s, 1H), 4.88 (m, 2H), 3.66 (m, 2H), 2.68 and 2.34 (m, 2H, rotamers); LCMS [M+H]: 403.

Workup

  1. dissolutiondissolution of the reagents
  2. additionwere added
  3. extractionthe aqueous layer extracted with EtOAc (50 mL)
  4. customThe organic layer was separated
  5. washwashed with brine (2×10 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give the crude product
  10. customThe crude product was purified

Sources & evidence

ORD record
ord-421914ad55be43d1b72763fc1c5a59b0
Source dataset
uspto-grants-2012_09
Patent number
US08263610B2

Reaction notes

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