Triethylamine → 2-(4-(4-Fluorobenzoyl)piperidin-1-yl)-N-((4-oxo-4,5,7,8-tetrahydro-3H-pyrano[4,3-d]pyrimidin-2-yl)methyl)acetamide

HRID 713473Notes

Reaction equation

HRID 713473 reaction equation
[NH2:1][CH2:2][C:3]1[NH:4][C:5](=[O:13])[C:6]2[CH2:12][O:11][CH2:10][CH2:9][C:7]=2[N:8]=1.[F:14][C:15]1[CH:32]=[CH:31][C:18]([C:19]([CH:21]2[CH2:26][CH2:25][N:24]([CH2:27][C:28](O)=[O:29])[CH2:23][CH2:22]2)=[O:20])=[CH:17][CH:16]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>ClCCl>[F:14][C:15]1[CH:16]=[CH:17][C:18]([C:19]([CH:21]2[CH2:22][CH2:23][N:24]([CH2:27][C:28]([NH:1][CH2:2][C:3]3[NH:4][C:5](=[O:13])[C:6]4[CH2:12][O:11][CH2:10][CH2:9][C:7]=4[N:8]=3)=[O:29])[CH2:25][CH2:26]2)=[O:20])=[CH:31][CH:32]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 712264022-(4-(4-Fluorobenzoyl)piperidin-1-YL)acetic acidHCID 1357418942-(Aminomethyl)-7,8-dihydro-3H-pyrano[4,3-D]pyrimidin-4(5H)-one

Product 1

HCID 1362373022-(4-(4-Fluorobenzoyl)piperidin-1-yl)-N-((4-oxo-4,5,7,8-tetrahydro-3H-pyrano[4,3-d]pyrimidin-2-yl)methyl)acetamideYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-aminomethyl-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (1.7 g, 9.6 mmol) and 2-(4-(4-fluorobenzoyl)piperidin-1-yl)acetic acid (2.7 g, 10 mmol) in dichloromethane (50 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.2 g, 11 mmol), 1-hydroxybenzotriazole (1.5 g, 9.6 mmol) and triethylamine (4.0 mL, 29 mmol). The mixture was stirred at ambient temperature for 24 hours. The reaction mixture was washed with ammonium chloride solution, concentrated in vacuo and purified via flash column chromatography (ethyl acetate:hexane, 10:90 to 100:0, methanol:dichloromethane, 1:99 to 10:90) to provide the title compound (2.2 g, 54% yield). 1H NMR (400 MHz, CDC3) δ 11.12 (s, 1H), 8.07 (s, 1H), 7.99 (dd, J=9.0, 5.5 Hz, 2H), 7.18 (t, J=8.5 Hz, 2H), 4.58 (s, 2H), 4.41 (d, J=6.0 Hz, 2H), 3.97 (t, J=5.5 Hz, 2H), 3.22-3.35 (m, 1H), 3.10-3.22 (m, 2H), 2.94-3.07 (m, 2H), 2.66-2.75 (m, 2H), 2.31-2.48 (m, 2H), 1.80-1.99 (m, 4H). HRMS calculated for C22H23N4O4 429.1938. found (ESI, [M+H]+), 429.1925. MS m/z 429.3 (M+1), retention time=1.28 min.

Workup

  1. washThe reaction mixture was washed with ammonium chloride solution
  2. concentrationconcentrated in vacuo
  3. custompurified via flash column chromatography (ethyl acetate:hexane, 10:90 to 100:0, methanol:dichloromethane, 1:99 to 10:90)

Sources & evidence

ORD record
ord-239151c81ef3419bb890b7f1be1ece66
Source dataset
uspto-grants-2015_11
Patent number
US09181266B2

Reaction notes

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