Triethylamine → 1-[2-Chloro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-6-(3-[1,3]dioxolan-2-yl-5-methyl-phenoxy)-5-isopropyl-1H-pyrimidine-2,4-dione

HRID 426214Notes

Reaction equation

HRID 426214 reaction equation
F[C:2]1[CH:7]=[C:6]([CH2:8]O)[CH:5]=[C:4]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[N:3]=1.C(N(CC)CC)C.CS([Cl:31])(=O)=O.C([O:39][C:40]1[N:45]=[C:44]([O:46]CC2C=CC=CC=2)[C:43]([CH:54]([CH3:56])[CH3:55])=[C:42]([O:57][C:58]2[CH:63]=[C:62]([CH3:64])[CH:61]=[C:60]([CH:65]3[O:69][CH2:68][CH2:67][O:66]3)[CH:59]=2)[N:41]=1)C1C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].[I-].[Li+]>C(Cl)(Cl)Cl.ClCCl.CN(C=O)C>[Cl:31][C:2]1[CH:7]=[C:6]([CH2:8][N:41]2[C:42]([O:57][C:58]3[CH:63]=[C:62]([CH3:64])[CH:61]=[C:60]([CH:65]4[O:69][CH2:68][CH2:67][O:66]4)[CH:59]=3)=[C:43]([CH:54]([CH3:56])[CH3:55])[C:44](=[O:46])[NH:45][C:40]2=[O:39])[CH:5]=[C:4]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[N:3]=1

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 66321Lithium iodideHCID 59184650HCID 59184650, compoundHCID 591846532,4-Bis-benzyloxy-6-(3-[1,3]dioxolan-2-yl-5-methyl-phenoxy)-5-isopropyl-pyrimidine

Product 1

HCID 591847941-[2-Chloro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-6-(3-[1,3]dioxolan-2-yl-5-methyl-phenoxy)-5-isopropyl-1H-pyrimidine-2,4-dioneYield 57.2%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-fluoro-6-(p-methoxybenzylamino)-4-pyridine-methanol (790 mg, 2.84 mmol) in chloroform (28 ml) at 0° C. (ice bat), was added triethylamine (597 μl, 4.26 mmol) followed by methanesulfonyl chloride (256 μl, 3.41 mmol). After stirring for 1.5 hr., the mixture was diluted with dichloromethane, washed with aqueous saturated sodium bicarbonate solution, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was further dried in high vacuo and mixed with compound 8 (945 mg, 2.84 mmol), anhydrous powdered potassium carbonate (392 mg, 2.84 mmol), and lithium iodide (381 mg, 2.84 mmol). Anhydrous DMF (15 ml) was then added into the mixture and stirred for overnight at room temperature. The mixture was evaporated in vacuo. The residue was dissolved in methanol-dichloromethane (1:9), filtered through a celite pad, and the pad was washed with dichloromethane. The combined filtrate was evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, EA:hexanes (1:2)) to afford 963 mg (57%) of a white foam. 1H NMR (200 MHz, CDCl3) δ 1.11 (6H, d, J=7.0 Hz), 2.30 (3H, s), 2.72 (1H, m), 3.79 (3H, s), 3.93-4.06 (4H, m), 4.30 (2H, d, J=5.4 Hz), 4.67 (2H, s), 5.04 (1H, t, J=5.4 Hz), 5.67 (1H, s), 5.96 (1H, s), 6.36 (1H, s), 6.57 (1H, s), 6.79 (1H, s), 6.85 (2H, d, J=8.4 Hz), 7.01 (1H, s), 7.22 (2H, d, J=8.4 Hz), 9.01 (1H, s).

Workup

  1. washwashed with aqueous saturated sodium bicarbonate solution
  2. dry with materialdried with anhydrous magnesium sulfate
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe residue was further dried in high vacuo
  6. stirringstirred for overnight at room temperature
  7. customThe mixture was evaporated in vacuo
  8. dissolutionThe residue was dissolved in methanol-dichloromethane (1:9)
  9. filtrationfiltered through a celite pad
  10. washthe pad was washed with dichloromethane
  11. customThe combined filtrate was evaporated in vacuo
  12. customthe residue was purified by silica gel column chromatography (eluent, EA:hexanes (1:2))

Sources & evidence

ORD record
ord-16c7f40ddeb2407181158171f79cfa16
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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