Triethylamine → 2-chloro-1-(3-(4-methoxybenzyl)-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-7(6H)-yl)-2-phenylethanone

HRID 2383433Notes

Reaction equation

HRID 2383433 reaction equation
[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([CH2:7][N:8]2[C:12]3[N:13]=[CH:14][C:15]4[CH2:16][NH:17][CH2:18][CH2:19][C:20]=4[C:11]=3[CH:10]=[N:9]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[Cl:30][CH:31]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:32](Cl)=[O:33]>ClCCl>[Cl:30][CH:31]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:32]([N:17]1[CH2:16][C:15]2[CH:14]=[N:13][C:12]3[N:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:22][CH:21]=4)[N:9]=[CH:10][C:11]=3[C:20]=2[CH2:19][CH2:18]1)=[O:33]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 102902Chloro(phenyl)acetyl chlorideHCID 594904033-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine

Product 1

HCID 594904292-chloro-1-(3-(4-methoxybenzyl)-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-7(6H)-yl)-2-phenylethanoneYield 85.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine (1.536 g, 5.22 mmol) in anhydrous dichloromethane (20 mL) was added triethylamine (2.18 mL, 15.66 mmol) followed by 2-chloro-2-phenylacetyl chloride (90%, 1.05 mL, 6.52 mmol). The mixture was stirred at room temperature for 1 hour. The reaction was quenched by the addition of water (10 mL). The reaction mixture was extracted with dichloromethane (10 mL) and the organic layer washed with brine (2×10 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to give the crude product. The crude product was purified by flash column chromatography (SiO2, gradient from 40% EtOAc in hexanes to 50% EtOAc in hexanes) to give the desired product, 2-chloro-1-(3-(4-methoxybenzyl)-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-7(6H)-yl)-2-phenylethanone as an off-white solid (1.99 g, 85%). 1H NMR (400 MHz, DMSO-d6) δ 8.43/8.24 (s, 1H, rotamers), 8.15/8.12 (s, 1H, rotamers), 7.52 (m, 2H), 7.40 (m, 3H), 7.17 (m, 2H), 6.83 (m, 2H), 6.53/6.48 (s, 1H, rotamers), 5.56 (s, 2H), 5.02-4.70 (m, 2H), 3.84 (m, 2H), 3.68 (s, 3H), 3.11/2.67 (m, 2H, rotamers); LCMS [M+H]: 447.

Workup

  1. customThe reaction was quenched by the addition of water (10 mL)
  2. extractionThe reaction mixture was extracted with dichloromethane (10 mL)
  3. washthe organic layer washed with brine (2×10 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give the crude product
  8. customThe crude product was purified by flash column chromatography (SiO2, gradient from 40% EtOAc in hexanes to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-3ac243411d524104a9d1a22a900d4030
Source dataset
uspto-grants-2012_09
Patent number
US08263610B2

Reaction notes

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