1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → [4-(4-Bromophenyl)piperazin-1-yl](2,2-difluorocyclopropyl)methanone

HRID 340631노트

반응식

HRID 340631 반응식
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[F:14][C:15]1([F:21])[CH2:17][CH:16]1[C:18](O)=[O:19].CN(C)CCCN=C=NCC.CCN(C(C)C)C(C)C>CN(C=O)C.C(O)C.CCCCCCC>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:18]([CH:16]3[CH2:17][C:15]3([F:21])[F:14])=[O:19])[CH2:10][CH2:9]2)=[CH:6][CH:7]=1

참가 물질

8

반응물 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27356291-(4-Bromophenyl)piperazineHCID 27828232,2-Difluorocyclopropane-1-carboxylic acid

생성물 1

HCID 86692009[4-(4-Bromophenyl)piperazin-1-yl](2,2-difluorocyclopropyl)methanone

시약·촉매·용매 3

HCID 702Ethanol용매HCID 6228Dimethylformamide용매HCID 8900Heptane용매

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온도
50 °C

실험 절차

To a solution of 1-(4-bromophenyl)piperazine (2.53 g, 10.5 mmol) in DMF (10 mL) was added 2,2-difluorocyclopropanecarboxylic acid (1.92 g, 15.7 mmol) 1H-benzotriazol-1-ol (2.84 g, 21.0 mmol), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide (3.26 g, 21.0 mmol) and DIEA (7.31 mL, 42.0 mmol). The resulting mixture was stirred at 50° C. for 1 h. The reaction mixture was then quenched with saturated ammonium chloride solution, extracted with ethyl acetate, and concentrated in vacuo. Purification by chromatography on silica gel (0 to 75% EtOAc in hexanes, then 75 to 100% EtOAc in hexanes) provided the racemic compound. The racemate was then dissolved in 10% ethanol in heptane and the enantiomers were separated on an OD chiral column by eluting column with 30% ethanol in heptane. The first eluting peak was defined as enantiomer A and the second eluting peak was defined as enantiomer B. LCMS m/z 346.8 [M+H]+; 1H NMR (500 MHz, CD2Cl2) δ 7.37 (d, J=9.0 Hz, 2 H),6.80 (d, J=9.0 Hz, 2 H), 4.00-3.93 (m, 1 H),3.84-3.61 (m, 3 H),3.31-3.02 (m, 4 H),2.60-2.50 (m, 1 H),2.23-2.11 (m, 1 H),1.75-1.64 (m, 1 H).

후처리

  1. customThe reaction mixture was then quenched with saturated ammonium chloride solution
  2. extractionextracted with ethyl acetate
  3. concentrationconcentrated in vacuo
  4. customPurification by chromatography on silica gel (0 to 75% EtOAc in hexanes
  5. custom75 to 100% EtOAc in hexanes) provided the racemic compound
  6. customthe enantiomers were separated on an OD chiral column
  7. washby eluting column with 30% ethanol in heptane

출처 및 근거

ORD 기록
ord-b0ee99ca52a14c3397a245bbd1b807a5
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08895583B2

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