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

HRID 1744306노트

반응식

HRID 1744306 반응식
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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

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

실험 절차

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+).

후처리

  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)

출처 및 근거

ORD 기록
ord-b9f8959cfd4c47879a75b453e4ca3bfb
출처 데이터셋
uspto-grants-2006_03
특허 번호
US07015226B2

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