L-Malic Acid → HCID 131730219, compound

HRID 388512Notes

Reaction equation

HRID 388512 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]([N:18]3[CH2:23][CH2:22][CH:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)=[O:17])[CH:10]=2)[CH:5]=[CH:4][C:3]=1[NH:31][C:32]([CH2:34][C:35]1([CH2:38][C:39]([NH:41][C:42]2[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=2)=[O:40])[CH2:37][CH2:36]1)=[O:33].[C:49]([OH:57])(=[O:56])[C@H:50]([CH2:52][C:53]([OH:55])=[O:54])[OH:51]>C(O)C>[C:49]([OH:57])(=[O:56])[C@H:50]([CH2:52][C:53]([OH:55])=[O:54])[OH:51].[F:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]([N:18]3[CH2:19][CH2:20][CH:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:22][CH2:23]3)=[O:17])[CH:10]=2)[CH:5]=[CH:4][C:3]=1[NH:31][C:32]([CH2:34][C:35]1([CH2:38][C:39]([NH:41][C:42]2[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=2)=[O:40])[CH2:37][CH2:36]1)=[O:33]

Participants

4

Reactant 2

HCID 222656L-Malic AcidHCID 131730213HCID 131730213, compound

Product 1

HCID 131730219HCID 131730219, compoundYield 76.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

N-(2-Fluoro-4-{[2-({[4-(4-methylpiperazin-1-yl)piperidin-1-yl]carbonyl}amino)pyridin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxyamide (31.4 mg) was suspended in ethanol (0.317 ml). (2S)-Malic acid (5.7 mg) was added to the suspension at room temperature, and the mixture was stirred at 50° C. to form a solution. The reaction mixture was stirred at room temperature for 18 hours. The precipitate was collected by filtration and washed with ethanol (0.158 ml, 2 times). It was then dried under aeration at room temperature for 30 minutes, and dried with warm air at 60° C. for 1 day to give the title compound (26.0 mg, 68%) as white crystals.

Workup

  1. customto form a solution
  2. stirringThe reaction mixture was stirred at room temperature for 18 hours
  3. filtrationThe precipitate was collected by filtration
  4. washwashed with ethanol (0.158 ml, 2 times)
  5. customIt was then dried under aeration at room temperature for 30 minutes
  6. customdried
  7. temperaturewith warm air at 60° C. for 1 day

Sources & evidence

ORD record
ord-dfd5fed5d8f14f8e88a172257144ac34
Source dataset
uspto-grants-2013_02
Patent number
US08377938B2

Reaction notes

Loading…