Diisopropylethylamine → N-(3-(isoquinolin-3-yl)-4-methylphenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine

HRID 1890737Notes

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]=[N: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[N: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 7-benzyl-N-(3-(isoquinolin-3-yl)-4-methylphenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine (500 mg, 1.09 mmol) in dichloroethane (14 ml) is added DIEA (284 mg, 2.2 mmol) and 1-chloroethyl carbonochloridate (313 mg, 2.2 mmol). The reaction mixture is stirred at 90° C. for 12 hours, and cooled. The solvent is removed by rotary evaporation. The residue is redissolved in methanol (20 ml) and stirred at room temperature for 15 hours. After concentration, 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-tetrahydropyrido[3,4-d]pyrimidin-4-amine as a dark yellow solid. LC-MS m/z: 368.2 (M+1).

Workup

temperaturecooled
customThe solvent is removed by rotary evaporation
dissolutionThe residue is redissolved in methanol (20 ml)
stirringstirred at room temperature for 15 hours
concentrationAfter concentration
customthe crude product is purified by silica gel flash chromatography (eluted with 5% methanol in ethyl acetate)

Sources & evidence

ORD record: ord-ed470f0b1ad74493bb19c1dd7211eddf
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507491B2

Reaction notes

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