Potassium Cyanide → tert-butyl 1-(2-(7-cyano-2-oxoquinolin-1(2H)-yl)ethyl)piperidin-4-ylcarbamate

HRID 255171노트

반응식

HRID 255171 반응식
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:28])[N:9]2[CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][CH:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:16][CH2:15]2)=[CH:4][CH:3]=1.[C-:29]#[N:30].[K+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C(#N)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:29]([C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:28])[N:9]2[CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][CH:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:25])([CH3:26])[CH3:24])[CH2:16][CH2:15]2)=[CH:4][CH:3]=1)#[N:30]

참가 물질

6

반응물 3

HCID 9032Potassium CyanideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 60200428tert-butyl {1-[2-(7-bromo-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate2회

생성물 1

HCID 60200429tert-butyl 1-(2-(7-cyano-2-oxoquinolin-1(2H)-yl)ethyl)piperidin-4-ylcarbamate

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 6342Acetonitrile용매

실험 절차

A mixture of tert-butyl {1-[2-(7-bromo-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate (Intermediate 16) (9.85 g, 21.9 mmol) and potassium cyanide (2.14 g, 32.8 mmol) in dry acetonitrile (60 mL) was degassed and flushed with nitrogen three times. Tributyltinchloride (0.059 mmol, 1.13 mL of a 51.6 mM solution in heptane) was added, followed by 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (63 mg, 0.11 mmol) and tris(dibenzylideneacetone)dipalladium (0) (100 mg, 0.11 mmol) and it was degassed and flushed with nitrogen like above. The mixture was stirred for 30 minutes at room temperature and then degassed and flushed with nitrogen again. It was heated at 85° C. for 20 hours. The solvent was removed under reduced pressure and the residue taken up in dichloromethane (500 mL) and washed with water (200 mL). The aqueous phase was back-extracted once with dichloromethane (200 mL) and combined organic phases were dried over sodium sulfate. Solvent was removed under reduced pressure and the residue was crystallized from acetonitrile (60 mL) to give the product as a colorless solid, 6.57 g (76%), mp 202° C.

후처리

  1. customwas degassed
  2. customflushed with nitrogen three times
  3. additionTributyltinchloride (0.059 mmol, 1.13 mL of a 51.6 mM solution in heptane) was added
  4. customwas degassed
  5. customflushed with nitrogen like above
  6. customdegassed
  7. customflushed with nitrogen again
  8. temperatureIt was heated at 85° C. for 20 hours
  9. customThe solvent was removed under reduced pressure
  10. washwashed with water (200 mL)
  11. extractionThe aqueous phase was back-extracted once with dichloromethane (200 mL)
  12. dry with materialwere dried over sodium sulfate
  13. customSolvent was removed under reduced pressure
  14. customthe residue was crystallized from acetonitrile (60 mL)

출처 및 근거

ORD 기록
ord-dc07fae6b576432bb4f0c66337946e6d
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07875715B2

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