Triethylamine → (S)-tert-butyl 3-((3-cyano-8-fluoroisoquinolin-1-yl)amino)pyrrolidine-1-carboxylate

HRID 1476877노트

반응식

HRID 1476877 반응식
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[F:12])[CH:5]=[C:4]([C:13]#[N:14])[N:3]=1.CCN(CC)CC.[NH2:22][C@H:23]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24]1>CN1C(=O)CCC1>[C:13]([C:4]1[N:3]=[C:2]([NH:22][C@H:23]2[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24]2)[C:11]2[C:6]([CH:5]=1)=[CH:7][CH:8]=[CH:9][C:10]=2[F:12])#[N:14]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 854071tert-butyl (3S)-3-aminopyrrolidine-1-carboxylateHCID 903868251-Chloro-8-fluoroisoquinoline-3-carbonitrile

생성물 1

HCID 90387010(S)-tert-butyl 3-((3-cyano-8-fluoroisoquinolin-1-yl)amino)pyrrolidine-1-carboxylate수율 81%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
160 °C

실험 절차

To a suspension of 1-chloro-8-fluoroisoquinoline-3-carbonitrile (0.8 g, 3.88 mmol) and Et3N (0.78 g, 7.76 mmol) in NMP (5 mL) was added (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate (0.87 g, 4.66 mmol) at RT. The resulting mixture was heated at 160° C. for 30 minutes in a microwave reactor. The reaction was quenched with water and the mixture was extracted with EtOAc (3×30 mL). The organic phase was dried over Na2SO4 and concentrated in vacuo. The crude product was purified by column chromatography eluting with ethyl acetate and petroleum ether (EtOAc/PE=1:50-1:9 gradient) on silica gel to give the title compound (1.12 g, 81%). 1H NMR (400 MHz, CDCl3) δ ppm 7.56-7.52 (m, 1H), 7.44-7.42 (d, 1H, J=8.0 Hz), 7.29 (s, 1H), 7.21-7.18 (m, 1H), 6.47-6.43 (m, 1H), 4.73 (br s, 1H), 3.77-3.72 (dd, J1=6.4 Hz, J2=11.6 Hz, 1H), 3.48-3.19 (m, 3H), 2.26 (br s, 1H), 1.90 (br s, 1H), 1.41 (s, 9H); ESI-MS m/z [M+H-tert-butyl]+ 301.2.

후처리

  1. customThe reaction was quenched with water
  2. extractionthe mixture was extracted with EtOAc (3×30 mL)
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography
  6. washeluting with ethyl acetate and petroleum ether (EtOAc/PE=1:50-1:9 gradient) on silica gel

출처 및 근거

ORD 기록
ord-135c3ce5decd479ea301483974657220
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09402841B2

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