Hydrochloric Acid → Nilotinib Hydrochloride Monohydrate

HRID 72808

반응식

HRID 72808 반응식
[CH3:1][C:2]1[CH:26]=[CH:25][C:5]([C:6]([NH:8][C:9]2[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[C:11]([N:19]3[CH:23]=[C:22]([CH3:24])[N:21]=[CH:20]3)[CH:10]=2)=[O:7])=[CH:4][C:3]=1[NH:27][C:28]1[N:33]=[C:32]([C:34]2[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=2)[CH:31]=[CH:30][N:29]=1.[ClH:40]>CO>[OH2:7].[ClH:40].[CH3:1][C:2]1[CH:26]=[CH:25][C:5]([C:6]([NH:8][C:9]2[CH:14]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:12]=[C:11]([N:19]3[CH:23]=[C:22]([CH3:24])[N:21]=[CH:20]3)[CH:10]=2)=[O:7])=[CH:4][C:3]=1[NH:27][C:28]1[N:33]=[C:32]([C:34]2[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=2)[CH:31]=[CH:30][N:29]=1

참가 물질

4

반응물 2

HCID 313Hydrochloric AcidHCID 644241Nilotinib

생성물 1

HCID 16757572Nilotinib Hydrochloride Monohydrate

시약·촉매·용매 1

HCID 887Methanol용매

반응 조건

온도
46 °C

실험 절차

A 1 L, 4-neck, round-bottom flask equipped with a mechanical stirrer, a thermometer, heating/cooling capacity, and an addition funnel was charged in sequence with 4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide free base (10 g), methanol (250 mL), and 37% hydrochloric acid (1.85 g) under nitrogen purge. The mixture was heated to 42-50° C. and stirred for an additional minutes. The resulting solution was filtered through a polypropylene pad, while maintaining the batch temperature above 40° C. The clear solution was transferred under nitrogen atmosphere to another 1 L, 4-neck, round-bottom flask equipped with a mechanical stirrer, a thermometer, and heating/cooling capacity. The batch was stirred and cooled to 30° C. over a period of 30 minutes. Seeds (20 mg) were added at this temperature, and the batch was cooled to 23° C. over a period of 45 minutes. The batch was stirred for an additional 3 hours to obtain a thick white suspension. The suspension was cooled to −10° C. over a period of 1.5 hours and stirred for an additional 30 minutes. Any solid was collected by filtration and rinsed with cold (−10° C.) methanol (20 mL). The solid was dried at 50-55° C./10-20 torr for 8-16 hours to obtain 4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide monohydrochloride monohydrate salt form B (9.8 g) as a white solid.

후처리

  1. customA 1 L, 4-neck, round-bottom flask equipped with a mechanical stirrer
  2. temperaturea thermometer, heating/cooling capacity, and an addition funnel
  3. custompurge
  4. filtrationThe resulting solution was filtered through a polypropylene pad
  5. temperaturewhile maintaining the batch temperature above 40° C
  6. custom4-neck, round-bottom flask equipped with a mechanical stirrer
  7. temperaturea thermometer, and heating/cooling capacity
  8. stirringThe batch was stirred
  9. temperaturecooled to 30° C. over a period of 30 minutes
  10. additionSeeds (20 mg) were added at this temperature
  11. temperaturethe batch was cooled to 23° C. over a period of 45 minutes
  12. stirringThe batch was stirred for an additional 3 hours
  13. customto obtain a thick white suspension
  14. temperatureThe suspension was cooled to −10° C. over a period of 1.5 hours
  15. stirringstirred for an additional 30 minutes
  16. filtrationAny solid was collected by filtration
  17. washrinsed with cold (−10° C.) methanol (20 mL)
  18. customThe solid was dried at 50-55° C./10-20 torr for 8-16 hours

출처 및 근거

ORD 기록
ord-b7035257607f4ea59167499c4e87ec4f
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08829015B2

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