Trifluoroacetic acid → HCID 86732032, 화합물

HRID 527421노트

반응식

HRID 527421 반응식
[CH3:1][S:2][C:3]1[N:4]=[CH:5][C:6]2[CH:12]=[CH:11][C:10](=[O:13])[N:9]([C:14]3[CH:15]=[C:16]([NH:20][C:21](=O)[O:22]C(C)(C)C)[CH:17]=[CH:18][CH:19]=3)[C:7]=2[N:8]=1.[C:28](O)([C:30](F)(F)F)=O.C(Cl)(=O)C=C>C(Cl)Cl>[CH3:1][S:2][C:3]1[N:4]=[CH:5][C:6]2[CH:12]=[CH:11][C:10](=[O:13])[N:9]([C:14]3[CH:15]=[C:16]([NH:20][C:21](=[O:22])[CH:28]=[CH2:30])[CH:17]=[CH:18][CH:19]=3)[C:7]=2[N:8]=1

참가 물질

5

반응물 3

HCID 6422Trifluoroacetic acidHCID 13140Acryloyl chloride2회HCID 86732006tert-butyl (3-(2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate

생성물 1

HCID 86732032HCID 86732032, 화합물

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a suspension of tert-butyl (3-(2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate (51) (651 mg, 1.69 mmol) in 10 mL of DCM at RT was added 3 mL of TFA. The resulting homogeneous solution was stirred at RT for 1 h. It was concentrated under reduced pressure. The residue was in dissolved in 20 mL of DCM and cooled with an ice bath, then treated with DEIA (1.47 mL, 8.47 mmol) followed by acryloyl chloride (0.16 mL, 2.03 mmol). After 20 min at 0° C., additional acryloyl chloride (80 μL) was added in. The resulting mixture was stirred for 5 min, then quenched with 0.5 N NaOH (10 mL). The layers were separated and the water layer was extracted with 50 mL of DCM. The combined DCM extracts were washed with 2×5 mL of brine, dried over Na2SO4 and concentrated. The residue was stirred in 25 mL of EtOAc. The insoluble solid was filtered and dried to give 310 mg of N-(3-(2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide (11a). The filtrate was concentrated and purified on a silica gel column (35-100% EtOAc in hexanes) to give 140 mg of N-(3-(2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide (11a). m/z (ESI, +ve ion) 338.9 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.40 (1H, s), 8.95 (1H, s), 8.05 (1H, d, J=9.6 Hz), 7.68 (2H, m), 7.49 (1H, t, J=7.8 Hz), 7.04 (1H, d, J=8.2 Hz), 6.72 (1H, d, J=9.6 Hz), 6.46 (1H, dd, J=17.0, 10.2 Hz), 6.26 (1H, d, J=16.8 Hz), 5.78 (1H, d, J=9.6 Hz), 2.20 (3H, s).

후처리

  1. concentrationIt was concentrated under reduced pressure
  2. dissolutionin dissolved in 20 mL of DCM
  3. temperaturecooled with an ice bath
  4. additiontreated with DEIA (1.47 mL, 8.47 mmol)
  5. waitAfter 20 min at 0° C.
  6. stirringThe resulting mixture was stirred for 5 min
  7. customquenched with 0.5 N NaOH (10 mL)
  8. customThe layers were separated
  9. extractionthe water layer was extracted with 50 mL of DCM
  10. washThe combined DCM extracts were washed with 2×5 mL of brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated
  13. stirringThe residue was stirred in 25 mL of EtOAc
  14. filtrationThe insoluble solid was filtered
  15. customdried

출처 및 근거

ORD 기록
ord-d73e54105f5c477facf6c22c23c5f557
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346801B2

반응 노트

불러오는 중…