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Potassium bis(trimethylsilyl)amide → N-benzyl-2-(8,9-difluoro-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-N-isopropyl-acetamide

HRID 914712
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HRID 914712 반응식
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[F:11][C:12]1[C:32]([F:33])=[CH:31][C:15]2[N:16]3[C:20]([CH2:21][C:22](=[O:24])[NH:23][C:14]=2[CH:13]=1)=[N:19][N:18]=[C:17]3[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[CH2:34]([N:41]([CH:46]([CH3:48])[CH3:47])[C:42](=[O:45])[CH2:43]Br)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>CN(C=O)C>[CH2:34]([N:41]([CH:46]([CH3:48])[CH3:47])[C:42](=[O:45])[CH2:43][N:23]1[C:22](=[O:24])[CH2:21][C:20]2[N:16]([C:17]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[N:18][N:19]=2)[C:15]2[CH:31]=[C:32]([F:33])[C:12]([F:11])=[CH:13][C:14]1=2)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
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참가 물질

5

반응물 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 15216006N-benzyl-2-bromo-N-propan-2-ylacetamideHCID 589579408,9-difluoro-1-phenyl-4H,6H-2,3,6,10b-tetraaza-benzo[e]azulen-5-one

생성물 1

HCID 58957934N-benzyl-2-(8,9-difluoro-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-N-isopropyl-acetamide

시약·촉매·용매 1

HCID 6228
Dimethylformamide
용매
2회

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온도
0 °C

실험 절차

To a solution of KHMDS (0.5 M in THF, 16.6 mL, 8.33 mmol) at 0° C. was added 8,9-difluoro-1-phenyl-4H,6H-2,3,6,10b-tetraaza-benzo[e]azulen-5-one (Preparation 4(C) (2.0 g, 6.4 mmol) in DMF (20 mL). The reaction was stirred at 0° C. for 35 minutes, was cooled to −10° C., and a solution of N-benzyl-2-bromo-N-isopropyl-acetamide (Preparation 1 (C) (1.9 g, 7.0 mmol) in DMF (20 mL) was added. The reaction was stirred at −10C for 2 hours and at room temperature for 24 hours. The reaction was quenched with a pH 6.8 buffer and the aqueous solution was washed with EtOAc (3×). The combined organic solutions were washed with brine (4×), dried (Na2SO4), filtered and concentrated. Purification by medium pressure chromatography eluting with a solvent gradient (CH2Cl2 to 3% MeOH in CH2Cl2) provided 2.01 g of N-benzyl-2-(8,9-difluoro-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-N-isopropyl-acetamide. 1H NMR (CD2Cl2) δ 7.60-7.17 (m, 11H), 6.75 (q, 1H), 4.85-4.38 (m, 4H), 4.10 (q, 1H), 3.60 (q, 1H), 3.41 (s, 1H), 1.21 (q, 3H), 1.13 (q, 3H); MS 502.4 (M+1), 500.3 (M−1).

후처리

  1. temperaturewas cooled to −10° C.
  2. additionwas added
  3. stirringThe reaction was stirred at −10C for 2 hours
  4. waitat room temperature for 24 hours
  5. customThe reaction was quenched with a pH 6.8 buffer
  6. washthe aqueous solution was washed with EtOAc (3×)
  7. washThe combined organic solutions were washed with brine (4×)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by medium pressure chromatography
  12. washeluting with a solvent gradient (CH2Cl2 to 3% MeOH in CH2Cl2)

출처 및 근거

ORD 기록
ord-dc5deb89850d4c0fa0034196d8116fe4
출처 데이터셋
uspto-grants-2007_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07265104B2

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