Potassium Carbonate → 5-{3-[2-Fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl}-isophthalonitrile

HRID 426281Notes

Reaction equation

HRID 426281 reaction equation
[CH:1]([C:4]1[C:9](=[O:10])[NH:8][C:7](=[O:11])[NH:6][C:5]=1[C:12]([C:14]1[CH:15]=[C:16]([C:22]#[N:23])[CH:17]=[C:18]([CH:21]=1)[C:19]#[N:20])=[O:13])([CH3:3])[CH3:2].[F:24][C:25]1[CH:30]=[C:29]([CH2:31]OS(C)(=O)=O)[CH:28]=[C:27]([NH:37][CH2:38][C:39]2[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=2)[N:26]=1.[I-].[Li+].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(OCC)(=O)C>[F:24][C:25]1[CH:30]=[C:29]([CH2:31][N:6]2[C:5]([C:12]([C:14]3[CH:15]=[C:16]([C:22]#[N:23])[CH:17]=[C:18]([CH:21]=3)[C:19]#[N:20])=[O:13])=[C:4]([CH:1]([CH3:3])[CH3:2])[C:9](=[O:10])[NH:8][C:7]2=[O:11])[CH:28]=[C:27]([NH:37][CH2:38][C:39]2[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=2)[N:26]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 66321Lithium iodideHCID 59184646Methanesulfonic acid 2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl esterHCID 591846985-(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-isophthalonitrile

Product 1

HCID 591847025-{3-[2-Fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl}-isophthalonitrileYield 31%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution 5-(5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-isophthalonitrile (0.016 g, 0.0535 mmol), methanesulfonic acid 2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl ester (0.017 g, 0.0535 mmol), lithium iodide (0.0036 g, 0.0268 mmol) and potassium carbonate (0.0074 g, 0.0535 mmol) in DMF (0.5 mL) was stirred at 0° C. for 4 h, then warmed to rt overnight. Reaction mixture was diluted with ethyl acetate, washed with water (2×), dried (MgSO4) and concentrated. The resulting residue was purified by flash column chromatography (silica gel, 10 to 50% ethyl acetate/hexane), then by reverse phase HPLC (Phenomenex Synergi® column, 5 to 100% acetonitrile/H2O) to give an yellow solid (0.0091 g, 31%). 1H NMR (300 MHz, CD3OD): δ 8.31 (s, 2H), 8.13 (s, 1H), 7.25 (d, J=8.7 Hz, 2H), 6.86 (d, J=8.4 Hz, 2H), 5.79 (s, 1H), 5.74 (s, 1H), 5.17 (d, J=16.8 Hz, 1H), 4.20 (s, 2H), 4.13 (d, J=16.8 Hz, 1H), 3.75 (s, 3H), 2.2-2.0 (m, 1H), 1.12 (d, J=6.6 Hz, 3H), 1.07 (d, J=6.6 Hz, 3H). Mass spectrum: 553.1 (M+H)+.

Workup

  1. customReaction mixture
  2. washwashed with water (2×)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe resulting residue was purified by flash column chromatography (silica gel, 10 to 50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-5ddf003fd5d4484b80fbe02ed0c24817
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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