Dichloromethane → HCID 117812396, compound

HRID 1481866Notes

Reaction equation

HRID 1481866 reaction equation
[NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][N:21]([CH3:23])[CH3:22])[CH:15]=3)[C:9]2=[O:12])=[CH:4][C:3]=1[N:24]1[CH2:29][CH2:28][N:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[CH3:36])[CH2:26][CH2:25]1.ClCCl.C(N(CC)C(C)C)(C)C.[O:49]1[CH:53]=[CH:52][CH:51]=[C:50]1[C:54](Cl)=[O:55]>>[CH3:22][N:21]([CH2:20][C:16]1[CH:15]=[C:14]([CH:19]=[CH:18][CH:17]=1)[CH2:13][N:8]1[CH2:7][CH2:6][C:5]2[C:10](=[CH:11][C:2]([NH:1][C:54]([C:50]3[O:49][CH:53]=[CH:52][CH:51]=3)=[O:55])=[C:3]([N:24]3[CH2:25][CH2:26][N:27]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[CH3:36])[CH2:28][CH2:29]3)[CH:4]=2)[C:9]1=[O:12])[CH3:23]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 682422-Furancarbonyl chlorideHCID 81531DiisopropylethylamineHCID 89690418HCID 89690418, compound

Product 1

HCID 117812396HCID 117812396, compoundYield 13.3%

Procedure

In a 40 ml scintillation vial equipped with a magnetic stir bar and fitted with a nitrogen inlet, the 7-amino-2-(3-dimethylaminomethyl-benzyl)-6-(4-o-tolyl-piperazin-1-yl)-3,4-dihydro-2H-isoquinolin-1-one 11b (73.70 mg, 0.15 mmol) was taken up in clean, dry, reagent-grade dichloromethane (3.00 ml, 46.52 mmol) and the mixture was stirred at room temperature under nitrogen atmosphere until the solids were all in solution. To this stirred solution was then added the N,N-diisopropylethylamine (0.08 ml, 0.46 mmol) followed by the furan-2-carbonyl chloride (0.02 ml, 0.20 mmol) and the reaction was allowed to stir overnight. The reaction was quenched with 3 ml of 2N HCl. The product solution was diluted with 10 ml of water and 10 ml of dichloromethane. The layers were separated and the product was extracted using dichloromethane (3×10 ml). The organic phases were combined and washed with brine (1×25 ml) and the product solution was then dried over MgSO4. The solution was then filtered under vacuum and the collected solution was concentrated under reduced pressure. The resultant yellow oil was then purified using silica gel column chromatography, eluting 100% dichloromethane to 7.5% MeOH in dichloromethane. The product needed further purification and was subjected to reverse-phase HPLC, eluting a gradient of 30% MeOH in water to 100% MeOH over a 5 min period. Furan-2-carboxylic acid [2-(3-dimethylaminomethyl-benzyl)-1-oxo-6-(4-o-tolyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-7-yl]-amide 11c (11.30 mg, 0.02 mmol) was isolated as a white solid.

Workup

  1. customIn a 40 ml scintillation vial equipped with a magnetic stir bar
  2. customfitted with a nitrogen inlet
  3. customdry
  4. customThe reaction was quenched with 3 ml of 2N HCl
  5. additionThe product solution was diluted with 10 ml of water and 10 ml of dichloromethane
  6. customThe layers were separated
  7. extractionthe product was extracted
  8. washwashed with brine (1×25 ml)
  9. dry with materialthe product solution was then dried over MgSO4
  10. filtrationThe solution was then filtered under vacuum
  11. concentrationthe collected solution was concentrated under reduced pressure
  12. customThe resultant yellow oil was then purified
  13. washeluting 100% dichloromethane to 7.5% MeOH in dichloromethane
  14. custompurification
  15. washeluting a gradient of 30% MeOH in water to 100% MeOH over a 5 min period

Sources & evidence

ORD record
ord-cfdd22cfd7734cd0b6190a55465bcce5
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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