HCID 21073265, compound → HCID 21073471, compound

HRID 1373568Notes

Reaction equation

HRID 1373568 reaction equation
Cl.[Cl:2][C:3]1[C:8]([Cl:9])=[CH:7][CH:6]=[CH:5][C:4]=1[N:10]1[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][OH:19])[CH2:12][CH2:11]1.C([O:27][C:28]1[CH:37]=[CH:36][C:35]2[C:30](=[N:31][C:32](Cl)=[CH:33][CH:34]=2)[N:29]=1)C1C=CC=CC=1>C1COCC1>[Cl:2][C:3]1[C:8]([Cl:9])=[CH:7][CH:6]=[CH:5][C:4]=1[N:10]1[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][CH2:18][O:19][C:32]2[N:31]=[C:30]3[C:35]([CH:36]=[CH:37][C:28](=[O:27])[NH:29]3)=[CH:34][CH:33]=2)[CH2:14][CH2:15]1

Participants

4

Reactant 2

HCID 21073265HCID 21073265, compoundHCID 21073288HCID 21073288, compound

Product 1

HCID 21073471HCID 21073471, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-40 °C

Procedure

An intermediate compound, 2-Benzyloxy-7-{3-[4-(2,3-dichloro-phenyl)-piperazin-1-yl]-propoxy}-[1,8]naphthyridine, was produced as follows: To a suspension of 3-[4-(2,3-dichloro-phenyl)-piperazin-1-yl]-propan-1-ol hydrochloride (400 mg, 1.23 mmol) in THF (5 mL) cooled to −40° C. was added KOtBU (1 M in THF, 2.3 mL, 2.3 mmol, 1.9 equiv). The mixture became a cloudy solution. After stirring for 20 min at −40° C., 2-benzyloxy-7-chloro-[1,8]naphthyridine (333 mg, 1.23 mmol) was added as a solution in THF (8 mL) via cannula. The reaction was allowed to warm to 0° C. slowly over 1 h. The reaction was quenched with saturated NH4Cl and H2O and extracted with EtOAc. The organic layer was washed with saturated NaHCO3 and brine, dried over Na2SO4 and concentrated. Purification by liquid chromatography (CH2Cl2 to 2% MeOH/CH2Cl2) gave the title compound as a clear oil/foam (367 mg, 0.701 mmol, 57%). MS: APCI: M+1: 523.0 (Exact Mass: 522.16).

Workup

  1. temperatureto warm to 0° C. slowly over 1 h
  2. customThe reaction was quenched with saturated NH4Cl and H2O
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with saturated NaHCO3 and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customPurification by liquid chromatography (CH2Cl2 to 2% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-8678bd5f23024df0a66c22a06204ba1d
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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