Hydrochloric Acid → HCID 22346985, compound

HRID 897534Notes

Reaction equation

HRID 897534 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:29]3[CH2:34][CH2:33][N:32]([C:35](=[O:46])[CH2:36][N:37](C)[C:38](=O)OC(C)(C)C)[CH2:31][CH2:30]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([NH:20][C:21]4[CH:22]=[C:23]([CH3:27])[CH:24]=[CH:25][CH:26]=4)=[O:19])=[C:13]([F:28])[CH:12]=3)[C:3]=12.Cl>CC(C)=O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:29]3[CH2:34][CH2:33][N:32]([C:35](=[O:46])[CH2:36][NH:37][CH3:38])[CH2:31][CH2:30]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([NH:20][C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([CH3:27])[CH:22]=4)=[O:19])=[C:13]([F:28])[CH:12]=3)[C:3]=12

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 22347380HCID 22347380, compound

Product 1

HCID 22346985HCID 22346985, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
45 °C

Procedure

The crude tert-butyl N-{2-[4-(4-amino-3-{3-fluoro-4-[(3-toluidinocarbonyl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidino]-2-oxoethyl}-N-methylcarbamate (75 mg, 0.119 mmol) was dissolved in acetone (5 mL) then aqueous hydrochloric acid (6N, 1 mL) was slowly added. The reaction mixture was heated at 45° C. for 2.5 hours then concentrated under reduced pressure. The remaining residue was triturated with dichloromethane (25 mL) to yield a light yellow solid. Purification by RP-HPLC (Waters PrepLC 4000, flow rate: 10 mL/min. λ=254 nm Gradient: 10% to 30% acetonitrile/0.1M aqueous ammonium acetate gradient over 40 minutes; Deltapak C18, 300 A, 15 μm, 40×100 mm column) afforded N-[4-(4-amino-1-{1-[2-(methylamino)acetyl]-4-piperidyl}-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-fluorophenyl]-N′-(3-methylphenyl)urea as a white solid (40 mg, 0.075 mmol). HPLC-RT: 12.22 min. (flow rate: 1 mL/min λ=254 nm Gradient: 5% to 85% acetonitrile/0.1M aqueous ammonium acetate gradient over 20 min.; Deltapak C18, 300 A, 5 μm, 150×3.9 mm column); m/z (MH+)=532.1.

Workup

  1. concentrationthen concentrated under reduced pressure
  2. customThe remaining residue was triturated with dichloromethane (25 mL)
  3. customto yield a light yellow solid
  4. customPurification by RP-HPLC (Waters PrepLC 4000, flow rate: 10 mL/min. λ=254 nm Gradient

Sources & evidence

ORD record
ord-cb166e0f28e64b0980c8b24d2852dfd5
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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