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

HRID 919599Notes

Reaction equation

HRID 919599 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

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 594214494-chloro-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-oneHCID 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.

Workup

  1. extractionThe reaction mixture was extracted with EtOAc (3×15 mL)
  2. dry with materialthe combined EtOAc layer was dried over Na2SO4
  3. customevaporated in vacuo
  4. customto give the crude product which
  5. customwas purified by column chromatography (silica gel, gradient EtOAc in hexanes)

Sources & evidence

ORD record
ord-8ec34301b9b64aeb94f5617d1dc0d1c6
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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