Oxalyl chloride → HCID 58458939, compound

HRID 390342Notes

Reaction equation

HRID 390342 reaction equation
[CH2:1]([O:8][C:9]1[C:14](=[O:15])[N:13]([CH3:16])[C:12]([CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:11][C:10]=1[C:22](O)=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[F:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38][C:39](=[NH:42])[NH:40]O)=[CH:34][CH:33]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.O1CCOCC1.CN(C=O)C>[CH2:1]([O:8][C:9]1[C:14](=[O:15])[N:13]([CH3:16])[C:12]([CH:17]2[CH2:18][CH2:19][CH2:20][CH2:21]2)=[N:11][C:10]=1[C:22]1[O:23][N:42]=[C:39]([CH2:38][C:35]2[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=2)[N:40]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 58458905HCID 58458905, compoundHCID 178510821HCID 178510821, compound

Product 1

HCID 58458939HCID 58458939, compoundYield 63%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 5-(benzyloxy)-2-cyclopentyl-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid (0.33, 1 mmol) in CH2Cl2 (3 mL) was added a catalytic amount of DMF followed by 3 mL of a 2M solution of oxalyl chloride dissolved in CH2Cl2. The resulting yellow reaction mixture was stirred for 1 h and concentrated to give a yellow oil. The yellow oil was dissolved in 1,4-dioxane (9 mL) and added to a stirred solution of 2-(4-fluorophenyl)-N-hydroxyacetimidamide (0.18 g, 1.1 mmol) and DIEA (0.2 mL) in 1,4-dioxane (1 mL). After 4 h at room temperature, the reaction mixture was heated at 90° C. for 14 h. The mixture was cooled to room temperature and purified by flash column chromatography on a silica gel column using 7:1 hexanes/EtOAc as eluant to afford the title compound (0.29 g, 63% yield) as an off-white solid. 1HNMR (500 MHz, CDCl3) δ: 7.43-7.39 (2H, m), 7.33 (2H, dd, J=8.6, 5.2 Hz), 7.28-7.23 (3H, m), 7.00 (2H, t, J=8.6 Hz), 5.34 (2H, s), 4.14 (2H, s), 3.63 (3H, s), 3.21-3.14 (1H, m), 2.05-1.99 (4H, m), 1.88-1.80 (2H, m), 1.71-1.62 (2H, m). HRMS (M+H) calcd for C26H26N4O3F: 461.1989. found: 461.1979.

Workup

  1. concentrationconcentrated
  2. customto give a yellow oil
  3. waitAfter 4 h at room temperature
  4. temperatureThe mixture was cooled to room temperature
  5. custompurified by flash column chromatography on a silica gel column

Sources & evidence

ORD record
ord-4737d2c0eabe44bdb7e448d96fe9dd3d
Source dataset
uspto-grants-2013_02
Patent number
US08383639B2

Reaction notes

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