Potassium Carbonate → Tert-butyl 4-[(2-{[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclobutyl]methyl}-6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]piperazine-1-carboxylate

HRID 906428노트

반응식

HRID 906428 반응식
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]1([CH2:18][O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])[CH2:17][CH2:16][CH2:15]1)[CH:6]=[C:5]2[CH2:27][N:28]1[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]1.[CH:41]1([NH:44][C:45](=[O:63])[C:46]2[CH:51]=[C:50](B3OC(C)(C)C(C)(C)O3)[C:49]([CH3:61])=[C:48]([F:62])[CH:47]=2)[CH2:43][CH2:42]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Si:20]([O:19][CH2:18][C:14]1([CH2:13][N:7]2[CH:6]=[C:5]([CH2:27][N:28]3[CH2:29][CH2:30][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:32][CH2:33]3)[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:50]4[CH:51]=[C:46]([C:45](=[O:63])[NH:44][CH:41]5[CH2:42][CH2:43]5)[CH:47]=[C:48]([F:62])[C:49]=4[CH3:61])[CH:3]=3)[C:8]2=[O:12])[CH2:17][CH2:16][CH2:15]1)([C:23]([CH3:24])([CH3:26])[CH3:25])([CH3:22])[CH3:21]

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 21914563N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 67390960tert-Butyl 4-[(6-bromo-2-{[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclobutyl]methyl}-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]piperazine-1-carboxylate

생성물 1

HCID 67391526Tert-butyl 4-[(2-{[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclobutyl]methyl}-6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]piperazine-1-carboxylate수율 55%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
75 °C

실험 절차

A solution of tert-butyl 4-[(6-bromo-2-{[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclobutyl]methyl}-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]piperazine-1-carboxylate (Example 27c, 0.153 g) in DMF (4 mL) was treated with N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.077 g), Pd-118 (4.71 mg) and potassium carbonate (0.067 g) under nitrogen. The resulting mixture was stirred at 75° C. for 8 h. The reaction was partitioned between ethyl acetate and water. The aqueous was extracted with ethyl acetate (2×100 mL) before washing the organics with water (3×100 mL) and brine (3×100 mL). The organic was dried (MgSO4), filtered, and evaporated under reduced pressure to afford the crude product. The crude product was purified (SiO2 chromatography, elution with 30% ethyl acetate/isohexane) to afford the subtitle compound (0.099 g) as an oil.

후처리

  1. customThe reaction was partitioned between ethyl acetate and water
  2. extractionThe aqueous was extracted with ethyl acetate (2×100 mL)
  3. washbefore washing the organics with water (3×100 mL) and brine (3×100 mL)
  4. dry with materialThe organic was dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customto afford the crude product
  8. customThe crude product was purified
  9. wash(SiO2 chromatography, elution with 30% ethyl acetate/isohexane)

출처 및 근거

ORD 기록
ord-d03f84d99cd84cb2a9203627f8c1442b
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08012980B2

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