Maleic Acid → HCID 86586243, compound

HRID 897437Notes

Reaction equation

HRID 897437 reaction equation
[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]\[C:4]([OH:6])=[O:5].[NH2:9][C:10]1[N:15]=[CH:14][N:13]=[C:12]2[N:16]([CH:37]3[CH2:42][CH2:41][CH:40]([N:43]4[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]4)[CH2:39][CH2:38]3)[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][S:26]([C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)(=[O:28])=[O:27])=[C:21]([F:36])[CH:20]=3)[C:11]=12>C(O)C>[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]\[C:4]([OH:6])=[O:5].[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]\[C:4]([OH:6])=[O:5].[NH2:9][C:10]1[N:15]=[CH:14][N:13]=[C:12]2[N:16]([CH:37]3[CH2:38][CH2:39][CH:40]([N:43]4[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]4)[CH2:41][CH2:42]3)[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][S:26]([C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)(=[O:28])=[O:27])=[C:21]([F:36])[CH:20]=3)[C:11]=12

Participants

4

Reactant 2

HCID 444266Maleic AcidHCID 22347000HCID 22347000, compound

Product 1

HCID 86586243HCID 86586243, compoundYield 108.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 3-(4-amino-3-fluorophenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate T) (107 mg, 0.252 mmol) and 4-fluorobenzenesulfonyl chloride (49 mg, 0.252 mmol) in pyridine (2.5 mL) was heated at 40° C. for 20 h. Additional 4-fluorobenzenesulfonyl chloride (15 mg, 0.063 mmol and 10 mg, 0.051 mmol) was added over 24 h. The reaction mixture was concentrated under reduced pressure to give an orange oil (220 mg, 0.378 mmol). The crude oil was purified by preparative RP-HPLC (Gilson C18) using an ammonium acetate gradient/acetonitrile gradient to give N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-fluorophenyl)-4-fluoro-1-benzenesulfonamide (Intermediate U) as a white solid (220 mg). Maleic acid (55 mg, 0.474 mmol) and the free base N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-fluorophenyl)-4-fluoro-1-benzenesulfonamide (92 mg, 0.158 mmol) were dissolved in hot ethanol (3 mL). A precipitate formed upon cooling which was collected by filtration, and dried on the lyophilizer to give N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-fluorophenyl)-4-fluoro-1-benzenesulfonamide di maleate salt as a white solid (100 mg, 0.172 mmol). 1H NMR (DMSO-d6, 400 MHz) 10.42 (s, 1H), 8.23 (s, 1H), 7.86 (m, 2H), 7.41 (m, 5H), 6.16 (s, 4H), 4.67 (br m, 1H), 2.62 (br m, 6H), 2.01 (br m, 6H), 1.56 (br m, 2H); MH+ 583.6.

Workup

  1. customThe crude oil was purified by preparative RP-HPLC (Gilson C18)
  2. customto give N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-fluorophenyl)-4-fluoro-1-benzenesulfonamide (Intermediate U) as a white solid (220 mg)
  3. customA precipitate formed
  4. temperatureupon cooling which
  5. filtrationwas collected by filtration
  6. customdried on the lyophilizer

Sources & evidence

ORD record
ord-7f9fed660f724eba993211efebb54a50
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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