Diisopropylethylamine → N-(3-(isoquinolin-3-yl)-4-methylphenyl)-5,6,7,8-tetrahydro-2,6-naphthyridin-1-amine

HRID 1890756Notes

Reaction equation

C([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[C:21]([C:26]4[N:27]=[CH:28][C:29]5[C:34]([CH:35]=4)=[CH:33][CH:32]=[CH:31][CH:30]=5)[CH:20]=3)=[N:13][CH:12]=[CH:11][C:10]=2[CH2:9]1)C1C=CC=CC=1.CCN(C(C)C)C(C)C.C(Cl)(=O)OC(Cl)C>ClC(Cl)C>[CH:28]1[C:29]2[C:34](=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:35]=[C:26]([C:21]2[CH:20]=[C:19]([NH:18][C:14]3[C:15]4[CH2:16][CH2:17][NH:8][CH2:9][C:10]=4[CH:11]=[CH:12][N:13]=3)[CH:24]=[CH:23][C:22]=2[CH3:25])[N:27]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 6-benzyl-N-(3-(isoquinolin-3-yl)-4-methylphenyl)-5,6,7,8-tetrahydro-2,6-naphthyridin-1-amine (320 mg, 0.7 mmol) in dichloroethane is added DIEA (225 mg, 1.75 mmol) and 1-chloroethyl carbonochloridate (200 mg, 1.4 mmol). The reaction mixture is stirred at 90° C. for 12 hours. After cooling, the solvent is removed by rotary evaporation. The residue is redissolved in 20 ml of methanol and stirred at room temperature for 15 hours. After removing solvent, the crude product is purified by silica gel flash chromatography, eluted with 5% methanol in ethyl acetate to afford N-(3-(isoquinolin-3-yl)-4-methylphenyl)-5,6,7,8-tetrahydro-2,6-naphthyridin-1-amine as a light yellow solid. MS m/z 367.2 (M+1).

Workup

temperatureAfter cooling
customthe solvent is removed by rotary evaporation
dissolutionThe residue is redissolved in 20 ml of methanol
stirringstirred at room temperature for 15 hours
customAfter removing solvent
customthe crude product is purified by silica gel flash chromatography
washeluted with 5% methanol in ethyl acetate

Sources & evidence

ORD record: ord-7232470cbf9e4740a384245af9f3b880
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507491B2

Reaction notes

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