Diisopropylethylamine → (S)-4-((1-benzylpiperidin-3-yl)(methyl)amino)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one

Reaction equation

[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([NH:14][CH3:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:18]2[CH2:26][CH2:25][C:24](=[O:27])[NH:23][C:19]=2[N:20]=[CH:21][N:22]=1.CCN(C(C)C)C(C)C>>[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([N:14]([CH3:15])[C:17]2[C:18]3[CH2:26][CH2:25][C:24](=[O:27])[NH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Reactant 3

HCID 81531Diisopropylethylamine

HCID 594214494-chloro-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one

HCID 66569260(S)-1-benzyl-N-methylpiperidin-3-amine

Product 1

HCID 86706465(S)-4-((1-benzylpiperidin-3-yl)(methyl)amino)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-oneYield 56.9%

Procedure

A solution of (S)-1-benzyl-N-methylpiperidin-3-amine (0.2 g, 1.0 mmol), 4-chloro-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (90 mg, 0.5 mmol) and DIEA (253 mg, 2.0 mmol) was heated in a sealed tube at 100° C. overnight. The reaction mixture was cooled to rt and poured into ice water. The reaction mixture was extracted with EtOAc (3×15 mL) and the combined EtOAc layer was dried over Na2SO4, evaporated in vacuo to give the crude product which was purified by column chromatography (silica gel, gradient EtOAc in hexanes) to afford (100 mg, 29%) of the titled intermediate. 1H NMR (400 MHz, CD3OD): δ 7.97 (s, 1H), 7.33-7.26 (m, 5H), 4.60-4.57 (m, 1H), 4.01-3.99 (m, 2H), 3.53 (s, 2H), 2.92 (s, 3H), 2.58-2.53 (m, 3H), 2.25-2.21 (m, 1H), 2.07-2.01 (m, 2H), 1.76-1.69 (m, 2H), 1.43-1.33 (m, 3H). LC-MS: m/z [M+1]=451 & [M+23]: 473.