Sodium Iodide → [(S)-1-(6-Bromo-2-methoxy-naphthalen-1-ylmethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-carbamic acid tert-butyl ester

HRID 1481894노트

반응식

HRID 1481894 반응식
[C:1]([O:5][C:6](=[O:20])[NH:7][C@@H:8]1[C:14](=[O:15])[NH:13][C:12]2[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=2[NH:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Br:31][C:32]1[CH:33]=[C:34]2[C:39](=[CH:40][CH:41]=1)[C:38]([CH2:42]Cl)=[C:37]([O:44][CH3:45])[CH:36]=[CH:35]2.[Na+].[I-]>C1COCC1>[C:1]([O:5][C:6](=[O:20])[NH:7][C@@H:8]1[C:14](=[O:15])[N:13]([CH2:42][C:38]2[C:39]3[C:34](=[CH:33][C:32]([Br:31])=[CH:41][CH:40]=3)[CH:35]=[CH:36][C:37]=2[O:44][CH3:45])[C:12]2[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=2[NH:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

참가 물질

6

반응물 4

HCID 5238Sodium IodideHCID 7371226-Bromo-1-(chloromethyl)-2-methoxynaphthaleneHCID 2733832Lithium HexamethyldisilazideHCID 22881971tert-butyl N-[(3S)-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl]carbamate2회

생성물 1

HCID 72713836[(S)-1-(6-Bromo-2-methoxy-naphthalen-1-ylmethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-carbamic acid tert-butyl ester수율 72.8%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

To a solution of ((S)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl)-carbamic acid tert-butyl ester (Intermediate 2) (6.5 g, 23.48 mmol) in THF (100 mL) at −78° C. was added 1 M LiHMDS (4.7 g, 28 mL, 28 mmol). The cooling bath was removed and the mixture stirred at RT for 1 h. The mixture was cooled to −78° C. and a mixture of 6-bromo-1-chloromethyl-2-methoxy-naphthalene (8.0 g, 28.12 mmol) and NaI (4.2 g, 28.12 mmol) in dry THF (30 mL) was added dropwise. The cooling bath was removed and the mixture stirred at RT for 18 h. The mixture was diluted with saturated NH4Cl, extracted with ethyl acetate and the organic layer washed with water, brine, dried (Na2SO4) and concentrated to give a material which was purified by silica gel chromatography to afford the title compound (9 g, 72%) as a yellow solid. LC-MS: 528.0 (M+H).

후처리

  1. customThe cooling bath was removed
  2. temperatureThe mixture was cooled to −78° C.
  3. additionwas added dropwise
  4. customThe cooling bath was removed
  5. stirringthe mixture stirred at RT for 18 h
  6. additionThe mixture was diluted with saturated NH4Cl
  7. extractionextracted with ethyl acetate
  8. washthe organic layer washed with water, brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customto give a material which
  12. customwas purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-e7f62fef4e4644f281f37e7a031c19bf
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409888B2

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