Water → HCID 57867361, compound

HRID 1516289Notes

Reaction equation

HRID 1516289 reaction equation
[F:1][C@:2]1([CH3:20])[C:6]([OH:8])([CH3:7])[C@@H:5]([CH2:9][OH:10])[O:4][CH:3]1[N:11]1[CH:16]=[C:15]([CH3:17])[C:14](=[O:18])[NH:13][C:12]1=[O:19].C(=NC1CCCCC1)=NC1CCCCC1.[C:36]([O:40][C:41]([NH:43][C@@H:44]([CH3:48])[C:45](O)=[O:46])=[O:42])([CH3:39])([CH3:38])[CH3:37].O>O1CCCC1>[C:36]([O:40][C:41]([NH:43][C@@H:44]([CH3:48])[C:45]([O:10][CH2:9][C@@H:5]1[C:6]([OH:8])([CH3:7])[C@:2]([F:1])([CH3:20])[CH:3]([N:11]2[CH:16]=[C:15]([CH3:17])[C:14](=[O:18])[NH:13][C:12]2=[O:19])[O:4]1)=[O:46])=[O:42])([CH3:39])([CH3:38])[CH3:37]

Participants

6

Reactant 4

HCID 962WaterHCID 10868DicyclohexylcarbodiimideHCID 85082Tert-butoxycarbonylalanineHCID 57867386HCID 57867386, compound

Product 1

HCID 57867361HCID 57867361, compoundYield 46.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 1-((3R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3,4-dimethyltetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione (about 0.05 g, 0.17 mmol) in tetrahydrofuran (about 5 ml) was added N,N-dimethyl amino pyridine (about 0.06 g, 0.52 mmol), N,N′-methanediylidenedicyclohexanamine (about 0.071 g, 0.34 mmol) and (S)-2-(tert-butoxycarbonylamino)propanoic acid (about 0.09 g, 0.52 mmol) at about 0° C. and stirred at room temperature for about 1 hour. Completion of the reaction monitored by thin-layer chromatography and water added to the reaction mixture. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine and dried over sodium sulphate. Concentration under reduced pressure and purification by silica gel column chromatography using 1.5% methanol in dichloromethane as eluent furnished title compound (0.03 g) as a colorless solid. Yield: 46.8%; 1H NMR (300 MHz, CDCl3): δ 8.08 (bs, 1H), 7.23-7.22 (m, 1H), 6.37 (d, 1H, J=23.4 Hz), 4.95 (bs, 1H), 4.45-4.25 (m, 3H), 3.40-3.34 (m, 1H), 1.95 (s, 3H), 1.45 (d, 3H, J=22.8 Hz), 1.44 (s, 9H), 1.41 (m, 3H), 1.27 (s, 3H), ES Mass: [M+Na] 482 (100%).

Workup

  1. additionadded to the reaction mixture
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulphate
  5. concentrationConcentration
  6. customunder reduced pressure and purification by silica gel column chromatography

Sources & evidence

ORD record
ord-b69704e46d404b14a078238954c230a6
Source dataset
uspto-grants-2012_07
Patent number
US08227431B2

Reaction notes

Loading…