Cesium carbonate → 1-(7-Acetyl-5-chloroquinolin-8-yl)pyrrolidine-3-carbonitrile

HRID 1192600노트

반응식

HRID 1192600 반응식
FC(F)(F)S(O[C:7]1[C:8]([C:18](=[O:20])[CH3:19])=[CH:9][C:10]([Cl:17])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)(=O)=O.Cl.[NH:24]1[CH2:28][CH2:27][CH:26]([C:29]#[N:30])[CH2:25]1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:18]([C:8]1[C:7]([N:24]2[CH2:28][CH2:27][CH:26]([C:29]#[N:30])[CH2:25]2)=[C:16]2[C:11]([CH:12]=[CH:13][CH:14]=[N:15]2)=[C:10]([Cl:17])[CH:9]=1)(=[O:20])[CH3:19]

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 42614784Pyrrolidine-3-carbonitrile hydrochlorideHCID 58368658HCID 58368658, 화합물

생성물 1

HCID 583686301-(7-Acetyl-5-chloroquinolin-8-yl)pyrrolidine-3-carbonitrile수율 16%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
65 °C

실험 절차

A stirred mixture of 7-acetyl-5-chloroquinolin-8-yl trifluoromethanesulfonate (0.12 g, 0.34 mmol, from Example 47, Step 2), pyrrolidine-3-carbonitrile hydrochloride (0.054 g, 0.41 mmol), palladium acetate (1.5 mg, 0.0068 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6.3 mg, 0.010 mmol), and cesium carbonate (0.31 g, 0.95 mmol) in tetrahydrofuran (3 mL) was heated at 65° C. overnight. The mixture was cooled, diluted with dichloromethane and filtered. The filtrate was washed with brine, dried over MgSO4 and evaporated to dryness. The resulting residue was purified on silica gel (eluting with 0 to 5% MeOH in dichloromethane) to give the desired product (16 mg, 16%). LCMS calculated for C16H15ClN3O (M+H)+: m/z=300.1; Found: 300.0.

후처리

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. washThe filtrate was washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customThe resulting residue was purified on silica gel (eluting with 0 to 5% MeOH in dichloromethane)

출처 및 근거

ORD 기록
ord-aaaf1407e22e4f7fb92131cc7fd2c91b
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08680108B2

반응 노트

불러오는 중…