Potassium Carbonate → 3-chloro-N-[3-(4-chloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-ylmethoxy)-4-methyl-phenyl]-4-(2-hydroxy-ethylamino)-benzamide

HRID 2426111Notes

Reaction equation

HRID 2426111 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[NH:19][CH2:20][CH2:21][OH:22])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([OH:15])[CH:9]=1)=[O:6].C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][C:31]1[C:39]2[C:34](=[N:35][CH:36]=[N:37][C:38]=2[Cl:40])[N:33]([CH3:41])[N:32]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[NH:19][CH2:20][CH2:21][OH:22])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([O:15][CH2:30][C:31]2[C:39]3[C:34](=[N:35][CH:36]=[N:37][C:38]=3[Cl:40])[N:33]([CH3:41])[N:32]=2)[CH:9]=1)=[O:6]

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 575815813-bromomethyl-4-chloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidineHCID 575815943-chloro-4-(2-hydroxyethylamino)-N-(3-hydroxy-4-methyl-phenyl)-benzamide

Product 1

HCID 575815863-chloro-N-[3-(4-chloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-ylmethoxy)-4-methyl-phenyl]-4-(2-hydroxy-ethylamino)-benzamide

Procedure

A mixture of 3-chloro-4-(2-hydroxyethylamino)-N-(3-hydroxy-4-methyl-phenyl)-benzamide (34.2 mg, 0.11 mmol) and potassium carbonate (17.3 mg, 0.123 mmol) was stirred at room temperature for 30 minutes before 3-bromomethyl-4-chloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidine (25.4 mg, 0.097 mmole, Example 5) was added. The reaction was stirred at room temperature overnight and then concentrated under reduced pressure to remove dimethylformamide. The residue was dissolved in ethyl acetate, washed with water, dried and concentrated. The crude product was either used directly in the next step (described in Example 9) or purified by flash chromatography (silica gel, hexanes-ethyl acetate, 90/10 to 60/40) to give pure 3-chloro-N-[3-(4-chloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-ylmethoxy)-4-methyl-phenyl]-4-(2-hydroxy-ethylamino)-benzamide as a white solid. (Yield 22 mg).

Workup

  1. additionwas added
  2. concentrationconcentrated under reduced pressure
  3. customto remove dimethylformamide
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with water
  6. customdried
  7. concentrationconcentrated
  8. custompurified by flash chromatography (silica gel, hexanes-ethyl acetate, 90/10 to 60/40)

Sources & evidence

ORD record
ord-493309b4bff84813973e5da70c43fcd6
Source dataset
uspto-grants-2011_06
Patent number
US07968554B2

Reaction notes

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