Sodium Carbonate → (3aS,8aR)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one

HRID 539120노트

반응식

HRID 539120 반응식
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[C@H:15]4[C:16]5[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=5[CH2:22][C@H:14]4[O:13][C:12]3=[O:23])=[N:7][C:6]=12.[F:24][C:25]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[CH:27][C:26]=1[C:40]1[N:44]=[CH:43][N:42]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[N:41]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.CCOC(C)=O.O1CCOCC1>[F:24][C:25]1[CH:30]=[C:29]([C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[CH:9][C:8]([N:11]4[C@H:15]5[C:16]6[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=6[CH2:22][C@H:14]5[O:13][C:12]4=[O:23])=[N:7][C:6]=23)[CH:28]=[CH:27][C:26]=1[C:40]1[N:44]=[CH:43][N:42]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[N:41]=1

참가 물질

9

반응물 4

HCID 10340Sodium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 67034012HCID 67034012, 화합물HCID 67034386(3aS,8aR)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one

생성물 1

HCID 67034771(3aS,8aR)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one수율 28.7%

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

반응 조건

온도
80 °C

실험 절차

To (3aS,8aR)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one (100 mg, 0.269 mmol) were added 3-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazole (147 mg, 0.350 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (15.6 mg, 0.0269 mmol), Pd2 dba3 (12.3 mg, 0.0135 mmol), dioxane (1.2 mL) and 2M Na2CO3 (0.2 mL). The reaction was stirred for 2 hours at 80° C. in a sealed tube. After cooling, EtOAc and water were added. The organic phase was washed with brine and dried over MgSO4. The residue was purified by reverse phase chromatography (SP4, 12M, water/CH3CN 90:10 to 0:100, 20 column volumes) to yield (3aS,8aR)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one (45 mg, 28.6% yield) as a pale yellow solid.

후처리

  1. temperatureAfter cooling
  2. washThe organic phase was washed with brine
  3. dry with materialdried over MgSO4
  4. customThe residue was purified by reverse phase chromatography (SP4, 12M, water/CH3CN 90:10 to 0:100, 20 column volumes)

출처 및 근거

ORD 기록
ord-06eeb33fc1c04beeaaec7fcabb20044f
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865726B2

반응 노트

불러오는 중…