Sodium cyanoborohydride → 4-(1-Acetylazetidin-3-yl)-7-chloro-6-fluoro-2-methyl-9-(2-methyl-1,3-dioxolan-2-yl)-4,5-dihydro-1,4-benzoxazepin-3(2H)-one

HRID 626861노트

반응식

HRID 626861 반응식
[Cl:1][C:2]1[CH:15]=[C:14]([C:16]2([CH3:21])[O:20][CH2:19][CH2:18][O:17]2)[C:5]([O:6][CH:7]([CH3:13])[C:8](OCC)=[O:9])=[C:4]([CH:22]=O)[C:3]=1[F:24].C([BH3-])#N.[Na+].Cl.[C:30]([N:33]1[CH2:36][CH:35]([NH2:37])[CH2:34]1)(=[O:32])[CH3:31]>CO>[C:30]([N:33]1[CH2:36][CH:35]([N:37]2[CH2:22][C:4]3[C:3]([F:24])=[C:2]([Cl:1])[CH:15]=[C:14]([C:16]4([CH3:21])[O:20][CH2:19][CH2:18][O:17]4)[C:5]=3[O:6][CH:7]([CH3:13])[C:8]2=[O:9])[CH2:34]1)(=[O:32])[CH3:31]

참가 물질

5

반응물 3

HCID 5003444Sodium cyanoborohydrideHCID 848193311-(3-Aminoazetidin-1-yl)ethanone hydrochlorideHCID 86697551Ethyl 2-[4-chloro-3-fluoro-2-formyl-6-(2-methyl-1,3-dioxolan-2-yl)phenoxy]propanoate

생성물 1

HCID 866975524-(1-Acetylazetidin-3-yl)-7-chloro-6-fluoro-2-methyl-9-(2-methyl-1,3-dioxolan-2-yl)-4,5-dihydro-1,4-benzoxazepin-3(2H)-one수율 32%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

A solution of ethyl 2-[4-chloro-3-fluoro-2-formyl-6-(2-methyl-1,3-dioxolan-2-yl)phenoxy]propanoate (392 mg, 1.09 mmol) in methanol (21 mL) was treated with sodium cyanoborohydride (171 mg, 2.72 mmol) followed by 1-acetylazetidin-3-amine hydrochloride (360 mg, 2.39 mmol) and stirred at room temperature overnight. The reaction mixture was quenched with acetic acid (200 μL) and concentrated in vacuo. The residue was diluted with toluene (60 mL) and heated at 110° C. for 2 h. The solvent was concentrated in vacuo, and the residue was purified via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (142 mg, 32%) as a mixture of enantiomers. LCMS calculated for C19H23ClFN2O5(M+H)+: m/z=413.1; found: 413.1.

후처리

  1. customThe reaction mixture was quenched with acetic acid (200 μL)
  2. concentrationconcentrated in vacuo
  3. additionThe residue was diluted with toluene (60 mL)
  4. temperatureheated at 110° C. for 2 h
  5. concentrationThe solvent was concentrated in vacuo
  6. customthe residue was purified via preparative LCMS (XBridge C18 column
  7. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

출처 및 근거

ORD 기록
ord-1a82ff885e944fcf80edb4804d8e9719
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309251B2

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