Isopropanol → SHR-1258 dimaleate

HRID 626390Notes

Reaction equation

HRID 626390 reaction equation
[CH3:1][CH2:2][O:3][C:4]1[CH:9]=[C:8]2[N:10]=[CH:11][C:12]([C:30]#[N:31])=[C:13]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]4[N:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[C:17]([Cl:29])[CH:16]=3)[C:7]2=[CH:6][C:5]=1[NH:32][C:33](/[CH:35]=[CH:36]/[C@@H:37]1[N:41]([CH3:42])[CH2:40][CH2:39][CH2:38]1)=[O:34].[C:43]([OH:50])(=[O:49])/[CH:44]=[CH:45]\[C:46]([OH:48])=[O:47].C(O)(C)C>>[CH3:1][CH2:2][O:3][C:4]1[CH:9]=[C:8]2[C:7]([C:13]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]4[N:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[C:17]([Cl:29])[CH:16]=3)=[C:12]([C:30]#[N:31])[CH:11]=[N:10]2)=[CH:6][C:5]=1[NH:32][C:33](/[CH:35]=[CH:36]/[C@H:37]1[CH2:38][CH2:39][CH2:40][N:41]1[CH3:42])=[O:34].[CH:44](/[C:43]([OH:50])=[O:49])=[CH:45]/[C:46]([OH:48])=[O:47].[CH:44](/[C:43]([OH:50])=[O:49])=[CH:45]/[C:46]([OH:48])=[O:47]

Participants

4

Reactant 3

HCID 3776IsopropanolHCID 444266Maleic AcidHCID 51039030Pyrotinib

Product 1

HCID 72710866SHR-1258 dimaleateYield 60.8%

Procedure

1.0 g of SHR1258 (prepared according to PCT Patent Application Publication WO2011029265) and 0.4 g of maleic acid were dissolved in 25 ml of isopropyl alcohol by heating. A solid was present while refluxing. After removing from heating, the obtained mixture was stirred to cause a precipitate. The resulting precipitate was collected by filtration and then dried at 45° C. under vacuum overnight to obtain 0.85 g of SHR1258 dimaleate crystal. Yield: 60%. X-ray diffraction pattern is shown in FIG. 1 in which there are characteristic peaks at 6.28 (14.06), 6.74 (13.10), 10.60 (8.34), 11.58 (7.64), 13.50 (6.55), 14.90 (5.94), 15.80 (5.60), 18.26 (4.85), 20.66 (4.30), 21.14 (4.20), 22.96 (3.87), 24.34 (3.65), 25.54 (3.49), and 26.12 (3.41). The DSC pattern is shown in FIG. 2, with a sharp heat absorption peak at 131.429° C. The crystal was defined as form I crystal.

Workup

  1. temperatureby heating
  2. temperaturewhile refluxing
  3. customAfter removing
  4. temperaturefrom heating
  5. filtrationThe resulting precipitate was collected by filtration
  6. customdried at 45° C. under vacuum overnight

Sources & evidence

ORD record
ord-a269d03504514693b87059e91c8c4fc7
Source dataset
uspto-grants-2016_04
Patent number
US09309226B2

Reaction notes

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