Oxalyl chloride → 2-{1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-N-(4-methoxy-benzyl)-acetamide

HRID 2194769Notes

Reaction equation

HRID 2194769 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([CH3:30])[CH:29]=1)[C:6]([C:8]1[N:13]([CH2:14][C:15]2([CH2:18][C:19](O)=[O:20])[CH2:17][CH2:16]2)[C:12](=[O:22])[NH:11][C:10](=[O:23])[C:9]=1[CH:24]([CH3:26])[CH3:25])=[O:7])#[N:2].C(Cl)(=O)C(Cl)=O.[CH3:37][O:38][C:39]1[CH:46]=[CH:45][C:42]([CH2:43][NH2:44])=[CH:41][CH:40]=1>C1COCC1.CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([CH3:30])[CH:29]=1)[C:6]([C:8]1[N:13]([CH2:14][C:15]2([CH2:18][C:19]([NH:44][CH2:43][C:42]3[CH:45]=[CH:46][C:39]([O:38][CH3:37])=[CH:40][CH:41]=3)=[O:20])[CH2:16][CH2:17]2)[C:12](=[O:22])[NH:11][C:10](=[O:23])[C:9]=1[CH:24]([CH3:26])[CH3:25])=[O:7])#[N:2]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 754524-MethoxybenzylamineHCID 25215194{1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-acetic acid

Product 1

HCID 582034682-{1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-N-(4-methoxy-benzyl)-acetamideYield 83.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of {1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-acetic acid (90 mg, 0.22 mmol) in THF (5 mL) cooled in an ice bath, were added oxalyl chloride (38 μL, 0.44 mmol) and one drop of DMF. After stirring for 1 hr., the mixture was evaporated in vacuo. The residue was dissolved in THF (8 mL) and p-methoxy benzylamine (261 μL, 2 mmol) was added. After stirring for 1 hr., the mixture was evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane (2:1): Rf=0.25 fraction was collected) to give 97 mg (83%) of 2-{1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-N-(4-methoxy-benzyl)-acetamide (84) as a white solid. 1H-NMR (200 MHz, CDCl3) δ 0.40-0.46 (4H, m), 1.12 (3H, d, J=6.6 Hz), 1.23 (3H, d, J=6.6 Hz), 2.00 (1H, d, J=15.4 Hz), 2.25 (1H, m), 2.48-2.55 (4H, m), 3.45 (1H., d, J=15.4 Hz), 3.80 (3H, s), 3.90 (1H, d, J=15.4 Hz), 4.34-4.39 (2H, m), 6.69 (1H, m), 6.83-6.90 (2H, m), 7.22-7.30 (2H, m), 7.81 (1H, s), 8.01 (1H, s), 8.07 (1H, s), 9.81 (1H, s).

Workup

  1. custom, the mixture was evaporated in vacuo
  2. dissolutionThe residue was dissolved in THF (8 mL)
  3. stirringAfter stirring for 1 hr
  4. custom, the mixture was evaporated in vacuo
  5. customthe residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane (2:1): Rf=0.25 fraction was collected)

Sources & evidence

ORD record
ord-9cc80b76d8de48018ab2116a4b0226ca
Source dataset
uspto-grants-2012_12
Patent number
US08334295B2

Reaction notes

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