Water → HCID 70912562, compound

HRID 1526132Notes

Reaction equation

HRID 1526132 reaction equation
[H-].[Na+].[C:3]([C:5]1[C:14]([S:15][CH3:16])=[N:13][C:12]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)=[C:11]2[C:6]=1[C:7]1[CH:29]=[CH:28][C:27]([N:30]3[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]3)=[CH:26][C:8]=1[NH:9][C:10]2=[O:25])#[N:4].I[CH2:44][CH3:45].O>O1CCCC1.CN(C)C=O>[C:3]([C:5]1[C:14]([S:15][CH3:16])=[N:13][C:12]([C:17]2[CH:18]=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=2)=[C:11]2[C:6]=1[C:7]1[CH:29]=[CH:28][C:27]([N:30]3[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]3)=[CH:26][C:8]=1[N:9]=[C:10]2[O:25][CH2:44][CH3:45])#[N:4].[C:3]([C:5]1[C:14]([S:15][CH3:16])=[N:13][C:12]([C:17]2[CH:18]=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=2)=[C:11]2[C:6]=1[C:7]1[CH:29]=[CH:28][C:27]([N:30]3[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]3)=[CH:26][C:8]=1[N:9]([CH2:44][CH3:45])[C:10]2=[O:25])#[N:4]

Participants

8

Reactant 4

HCID 962WaterHCID 6340IodoethaneHCID 24758Sodium hydrideHCID 70874291HCID 70874291, compound

Product 2

HCID 70874372HCID 70874372, compoundYield 24%HCID 70912562HCID 70912562, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

75 mg (1.86 mmol) of sodium hydride 60% dispersion in oil is added to 0.52 g (1.93 mmol) of tert-butyl 4-(1-cyano-4-(4-methoxyphenyl)-2-(methylthio)-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)piperazine-1-carboxylate dissolved in 14 ml of tetrahydrofuran and 17 ml of anhydrous dimethylformamide. The reaction medium is carried at 60° C. for 45 minutes before the addition of 127 μl (1.86 mmol) of hot iodoethane solution. The reaction mixture is stirred at 60° C. for additional 25 minutes. After returning to room temperature, water is added and then the product is extracted several times with ethyl acetate. The organic phases are combined, washed with saturated sodium chloride solution, dried on magnesium sulfate and concentrated. The residue is purified by silica gel chromatography (eluent: 7:3 cyclohexane/ethyl acetate) to yield 130 mg (24%) of tert-butyl 4-(1-cyano-5-ethoxy-4-(4-methoxyphenyl)-2-(methylthio)benzo[c][2,7]naphthyridin-8-yl)piperazine-1-carboxylate in the form of a yellow solid and 360 mg (56%) of tert-butyl 4-(1-cyano-6-ethyl-4-(4-methoxyphenyl)-2-(methylthio)-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)piperazine-1-carboxylate in the form of a yellow solid.

Workup

  1. customAfter returning to room temperature
  2. extractionthe product is extracted several times with ethyl acetate
  3. washwashed with saturated sodium chloride solution
  4. customdried on magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue is purified by silica gel chromatography (eluent: 7:3 cyclohexane/ethyl acetate)

Sources & evidence

ORD record
ord-916b169cce9449289b23992639818e95
Source dataset
uspto-grants-2015_07
Patent number
US09085575B2

Reaction notes

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