Water → Pelitinib

HRID 1167145노트

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HRID 1167145 반응식
[CH3:1][N:2]1[C:6](=[O:7])[CH2:5][CH2:4][CH2:3]1.[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:28][CH2:29][CH3:30])=[C:24]([NH2:27])[CH:25]=3)[N:20]=[CH:19][C:18]=2[C:31]#[N:32])[CH:12]=[CH:13][C:14]=1[F:15].O.[C:34](=O)(O)[O-].[Na+]>CN1C(=O)CCC1.CC#N>[CH3:30][CH2:29][O:28][C:23]1[CH:22]=[C:21]2[N:20]=[CH:19][C:18]([C:31]#[N:32])=[C:17]([NH:16][C:11]3[CH:12]=[CH:13][C:14]([F:15])=[C:9]([Cl:8])[CH:10]=3)[C:26]2=[CH:25][C:24]=1[NH:27][C:6](/[CH:5]=[CH:4]/[CH2:3][N:2]([CH3:1])[CH3:34])=[O:7]

참가 물질

6

반응물 4

HCID 962WaterHCID 13387N-methyl-2-pyrrolidoneHCID 516892Sodium BicarbonateHCID 110356856-Amino-4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethyloxyquinoline

생성물 1

HCID 6445562Pelitinib수율 86%

시약·촉매·용매 1

HCID 19934284Nmp CH3CN용매

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온도
42.5 °C

실험 절차

A 3 L multi-neck flask was equipped with an agitator, thermometer, dip tube, and nitrogen protection. The flask was charged with N-methyl pyrrolidinone (0.77 kg, 0.75 L, d=1.033 g/mL). At ambient temperature, 4-[3-chloro-4-fluorophenyl]amino-6-amino-3-cyano-7-ethoxy quinoline (0.0748 kg) [see, U.S. Pat. No. 6,002,008] was added and the mixture stirred while heating to 40-45° C. and hold for 15 min. The flask was cooled to 0-10° C. The mixture containing 4-N,N-dimethylaminocrotonoyl chloride hydrochloride was transferred via dip tube and positive nitrogen pressure to the 3 L flask over 30-45 min, while maintaining 0-10° C. The mixture was kept at 0-10° C. for a minimum of 2 h. The reaction was checked for completion by HPLC. The reaction is complete when there is ≦2% of the starting material (4-[3-chloro-4-fluorophenyl]amino-6-amino-3-cyano-7-ethoxy quinoline) present. A 12 L multi-neck flask equipped with agitator, thermometer, dip tube, and nitrogen protection was charged with water (2.61 kg, 2.61 L). Sodium bicarbonate (0.209 kg) was added and stirred until a solution was obtained. The solution was cooled to 20-24° C. The NMP-CH3CN mixture was transferred, via dip tube and positive nitrogen pressure, to the 12 L flask over 45-60 min, while maintaining 20-24° C. The mixture was maintained at 20-24° C. for a minimum of 1 h, and filtered on a Buchner funnel, and rinsed with water (3×0.40 kg, 3×0.40 L) with suction being maintained until dripping stops. The product was dried in a vacuum oven at 50° C. and 10 mm Hg for 28-30 h to give 78.5 g (86% yield) of product.

후처리

  1. customA 3 L multi-neck flask was equipped with an agitator
  2. customAt ambient temperature
  3. addition6,002,008] was added
  4. temperatureThe flask was cooled to 0-10° C
  5. customwas transferred via dip tube
  6. waitpositive nitrogen pressure to the 3 L flask over 30-45 min
  7. temperaturewhile maintaining 0-10° C
  8. customwas kept at 0-10° C. for a minimum of 2 h
  9. customA 12 L multi-neck flask equipped with agitator
  10. stirringstirred until a solution
  11. customwas obtained
  12. temperatureThe solution was cooled to 20-24° C
  13. waitpositive nitrogen pressure, to the 12 L flask over 45-60 min
  14. temperaturewhile maintaining 20-24° C
  15. temperatureThe mixture was maintained at 20-24° C. for a minimum of 1 h
  16. filtrationfiltered on a Buchner funnel
  17. washrinsed with water (3×0.40 kg, 3×0.40 L) with suction
  18. temperaturebeing maintained
  19. customThe product was dried in a vacuum oven at 50° C.

출처 및 근거

ORD 기록
ord-1dc442039f214e2bb7f9e5914e2fc7f8
출처 데이터셋
uspto-grants-2003_09
특허 번호
US06617333B2

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