Dimethylformamide → Camptosar

HRID 631180

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HRID 631180 반응식
[ClH:1].[OH2:2].O.O.CN(C)C=[O:8].[CH3:10][CH2:11][C:12]1[C:21]2[CH2:22][N:23]3[C:28](=[O:29])[C:27]4[CH2:30][O:31][C:32]([C@:34]([OH:37])([CH2:35][CH3:36])[C:26]=4[CH:25]=[C:24]3[C:20]=2[N:19]=[C:18]2[C:13]=1[CH:14]=[C:15]([O:38][C:39]([N:41]1[CH2:46][CH2:45][CH:44]([N:47]3[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]3)[CH2:43][CH2:42]1)=[O:40])[CH:16]=[CH:17]2)=[O:33]>CCCCCCC>[CH3:10][CH2:11][C:12]1[C:21]2[CH2:22][N:23]3[C:28](=[O:29])[C:27]4[CH2:30][O:31][C:32]([C@:34]([OH:37])([CH2:35][CH3:36])[C:26]=4[CH:25]=[C:24]3[C:20]=2[N:19]=[C:18]2[C:13]=1[CH:14]=[C:15]([O:38][C:39]([N:41]1[CH2:42][CH2:43][CH:44]([N:47]3[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]3)[CH2:45][CH2:46]1)=[O:40])[CH:16]=[CH:17]2)=[O:33].[OH2:8].[OH2:2].[OH2:8].[ClH:1]

참가 물질

5

반응물 3

HCID 6228Dimethylformamide3회HCID 60838IrinotecanHCID 21864422HCID 21864422, 화합물

생성물 1

HCID 60837Camptosar

시약·촉매·용매 1

HCID 8900Heptane용매2회

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온도
60 °C

실험 절차

HCl.3H2O (45.05 g, 66.52 mmol) was charged into a reactor. Anhydrous N,N-dimethylformamide (DMF) (666 mL, 14.7 mL/g of IRT.HCl.3H2O, DMF water content NMT 300 ppm) was charged to the reactor. With slow agitation, the reactor was heated to 60° C. (jacket temperature). After the irinotecan (IRT) was fully dissolved (5-10 minutes), vacuum was slowly applied to reach 5-10 mbar and DMF was distilled off. When the volume of condensed distillate (DMF) reached 85-90% of the initial DMF charge, the vacuum was released. Heptane (1330 mL, 30.0 mL/g of IRT.HCl.3H2O, water content NMT 50 ppm) was introduced into the reactor and the jacket temperature was lowered to 50° C. Heptane was vacuum distilled (100-150 mbar) until the volume of the distillate was about 90% of the initial charge of heptane. Two more cycles of heptane distillation were carried out (2×1330 mL heptane charge and distillation). A solvent phase sample was taken from the reactor and was analyzed for DMF content using GC to ensure a DMF content of less than 3% w/w. (In the event the residual DMF was >3.0% w/w, a fourth azeotropic distillation cycle would be performed). The resultant slurry was used for the coupling reaction (Part 2).

후처리

  1. distillationwas distilled off
  2. customWhen the volume of condensed distillate (DMF)
  3. additioncharge
  4. customwas lowered to 50° C
  5. distillationdistilled (100-150 mbar) until the volume of the distillate
  6. additioninitial charge of heptane
  7. distillationTwo more cycles of heptane distillation
  8. addition(2×1330 mL heptane charge and distillation)
  9. distillationa fourth azeotropic distillation cycle
  10. customThe resultant slurry was used for the coupling reaction (Part 2)

출처 및 근거

ORD 기록
ord-e1aca13c5a2d4d7da7e218b337b5af5e
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09320808B2

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