Diisopropylethylamine → (R)-1-(4-(6-benzyl-2-chloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-yl)ethanone

HRID 80780Notes

Reaction equation

[CH2:1]([N:8]1[CH2:19][CH2:18][C:11]2[N:12]=[C:13]([Cl:17])[N:14]=[C:15](Cl)[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.[CH3:27][C@H:28]1[NH:33][CH2:32][CH2:31][N:30]([C:34](=[O:36])[CH3:35])[CH2:29]1.CCN(C(C)C)C(C)C>CC(O)C.CCOC(C)=O>[CH2:1]([N:8]1[CH2:19][CH2:18][C:11]2[N:12]=[C:13]([Cl:17])[N:14]=[C:15]([N:33]3[CH2:32][CH2:31][N:30]([C:34](=[O:36])[CH3:35])[CH2:29][C@H:28]3[CH3:27])[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 6-benzyl-2,4-dichloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (0.655 g, 1.89 mmol), (R)-1-(3-methylpiperazin-1-yl)ethanone 2,2,2-trifluoroacetate (1 g, 2.84 mmol) and DIEA (2.65 mL, 15.2 mmol) in i-PrOH (25 mL) was heated to 80° C. for 48 h. The reaction mixture was then diluted with EtOAc, and washed successively with sat aq NaHCO3 and brine. The organic layer was then dried over Na2SO4, filtered and concentrated. The resulting residue was diluted with DCM and filtered to remove solid. The filtrate was concentrated and purified by FCC (0-5% MeOH in DCM) to provide (R)-1-(4-(6-benzyl-2-chloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-yl)ethanone. MS (ESI+) m/z 400.3 (M+H)+.

Workup

washwashed successively with sat aq NaHCO3 and brine
dry with materialThe organic layer was then dried over Na2SO4
filtrationfiltered
concentrationconcentrated
additionThe resulting residue was diluted with DCM
filtrationfiltered
customto remove solid
concentrationThe filtrate was concentrated
custompurified by FCC (0-5% MeOH in DCM)

Sources & evidence

ORD record: ord-2411be6a1dd2413d9b652ef68b704825
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846656B2

Reaction notes

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