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

HRID 1744306ノート

反応式

HRID 1744306 の反応式
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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

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

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-b9f8959cfd4c47879a75b453e4ca3bfb
出典データセット
uspto-grants-2006_03
特許番号
US07015226B2

反応ノート

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