Nitrogen → 5-(2-fluoro-3-methoxyphenyl)-1-[2,6-difluorobenzyl]-3-{3-hydroxy-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dione

HRID 1766048Notes

Reaction equation

HRID 1766048 reaction equation
Br[C:2]1[C:3](=[O:32])[N:4]([CH2:19][C@@H:20]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:21][O:22]C(=O)C)[C:5](=[O:18])[N:6]([CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])[C:7]=1[CH3:8].[F:33][C:34]1[C:39]([O:40][CH3:41])=[CH:38][CH:37]=[CH:36][C:35]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+].N#N>O1CCOCC1.O>[F:33][C:34]1[C:39]([O:40][CH3:41])=[CH:38][CH:37]=[CH:36][C:35]=1[C:2]1[C:3](=[O:32])[N:4]([CH2:19][C@@H:20]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:21][OH:22])[C:5](=[O:18])[N:6]([CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])[C:7]=1[CH3:8]

Participants

6

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 49857442-Fluoro-3-methoxyphenylboronic acidHCID 210183995-bromo-1-[2, 6-difluorobenzyl]-3-{3-acetoxy-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dione

Product 1

HCID 210183965-(2-fluoro-3-methoxyphenyl)-1-[2,6-difluorobenzyl]-3-{3-hydroxy-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dioneYield 66.9%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

To compound 8a (4.05 g, 8 mmol) in dioxane/water (100/50 mL) was added 2-fluoro-3-methoxyphenylboronic acid (2.04 g, 12 mmol) and Na2CO3 (5.08 g, 48 mmol). The reaction mixture was deoxygenated with N2 for 10 min, tetrakis(triphenylphosine) palladium (0) (924 mg, 0.8 mmol) was added and the reaction mixture was heated at 100° C. overnight under the protection of N2. The reaction mixture was partitioned between brine and EtOAc. The organic layer was dried (sodium sulfate), evaporated and purified by flash chromatography (silica, 50% EtOAc/hexanes) to give compound 8b (2.73 g, 66.9%). MS (CI) m/z 511.1 (MH+).

Workup

  1. customThe reaction mixture was deoxygenated with N2 for 10 min
  2. customThe reaction mixture was partitioned between brine and EtOAc
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. customevaporated
  5. custompurified by flash chromatography (silica, 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-24f02268efb844cea14a30ef7a4e46d2
Source dataset
uspto-grants-2007_06
Patent number
US07229995B2

Reaction notes

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