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

HRID 713474Notes

Reaction equation

HRID 713474 reaction equation
[Cl:1][C:2]1[CH:19]=[CH:18][C:5]([C:6]([CH:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]([OH:17])=O)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[NH2:49][CH2:50][C:51]1[NH:52][C:53](=[O:61])[C:54]2[CH2:60][O:59][CH2:58][CH2:57][C:55]=2[N:56]=1>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([CH:8]2[CH2:9][CH2:10][N:11]([CH2:14][C:15]([NH:49][CH2:50][C:51]3[NH:52][C:53](=[O:61])[C:54]4[CH2:60][O:59][CH2:58][CH2:57][C:55]=4[N:56]=3)=[O:17])[CH2:12][CH2:13]2)=[O:7])=[CH:18][CH:19]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 71227333[4-(4-Chloro-benzoyl)-piperidin-1-yl]-acetic acidHCID 1357418942-(Aminomethyl)-7,8-dihydro-3H-pyrano[4,3-D]pyrimidin-4(5H)-one

Product 1

HCID 1362373032-[4-(4-Chloro-benzoyl)-piperidin-1-yl]-N-(4-oxo-3,5,7,8-tetrahydro-4H-pyrano[4,3-d]-pyrimidin-2-ylmethyl)-acetamideYield 24%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of [4-(4-chloro-benzoyl)-piperidin-1-yl]-acetic acid (0.1 g, 0.36 mmol), EDCl (0.08 g, 0.43 mmol), HOBT (0.06 g, 0.43 mmol) and triethylamine (0.14 g, 1.4 mmol) in 20 mL of DMF, was stirred at ambient temperature for 20 min. then added 2-aminomethyl-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (0.08 g, 0.43 mmol). The reaction mixture was stirred at ambient temperature for 15 hours. The reaction mixture was diluted with 50 mL of water, extracted with DCM (20 mL). The combined organic layers were washed with saturated aqueous NaHCO3 solution. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo to provide crude product. Purification by flash chromatography gave the title compound (37.2 mg, 0.084 mmol, 24% yield) as a white solid. MS (ESI) m/z 445.2 (M+H+); HPLC (Novapak 150×3.9 mm C-18 column: mobile phase: 35-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 2 min.) t 1.12 min. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.61-1.83 (m, 6H), 2.21-2.30 (m, 1H), 2.50 (br. s., 2H), 2.94 (br. s., 1H), 2.99 (s, 2H), 3.32 (s, 2H), 3.35-3.46, (m, 1H), 3.83 (t, J=5.31 Hz, 1H), 4.19 (d, J=6.06 Hz, 1H), 4.34 (s, 2H), 7.60 (d, J=8.59 Hz, 2H), 8.00 (d, J=8.59 Hz, 2H), 8.20 (s, 1H) 12.40 (s, 1H). HRMS calculated for C22H26ClN4O4: 445.1643 (M+H). found (ESI, [M+H]+): 445.1658.

Workup

  1. extractionextracted with DCM (20 mL)
  2. washThe combined organic layers were washed with saturated aqueous NaHCO3 solution
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide crude product
  7. customPurification by flash chromatography

Sources & evidence

ORD record
ord-6286eaab80c946dc931fc12556311a7e
Source dataset
uspto-grants-2015_11
Patent number
US09181266B2

Reaction notes

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