Potassium Carbonate → 1-(4-methoxybenzyl)-4-(4-amino-5-chloro-2-fluorophenoxy)-N-(1-methylpiperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine

HRID 2241386Notes

Reaction equation

HRID 2241386 reaction equation
[CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[C:23]([F:24])=[CH:22][C:21]([NH2:25])=[C:20]([Cl:26])[CH:19]=4)=[C:11]3[C:10](I)=[N:9]2)=[CH:5][CH:4]=1.[NH2:30][CH:31]1[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]1.C([O-])([O-])=O.[K+].[K+].N1CCC[C@H]1C(O)=O>CS(C)=O.C(Cl)Cl.O>[CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:19]=[C:20]([Cl:26])[C:21]([NH2:25])=[CH:22][C:23]=4[F:24])=[C:11]3[C:10]([NH:30][CH:31]3[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]3)=[N:9]2)=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 27375314-Amino-1-methylpiperidineHCID 685133884-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-2-chloro-5-fluorobenzenamine

Product 1

HCID 685163031-(4-methoxybenzyl)-4-(4-amino-5-chloro-2-fluorophenoxy)-N-(1-methylpiperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-amineYield 66.9%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-2-chloro-5-fluorobenzenamine (200 mg, 0.38 mmol) was added into a suspension of 4-amino-1-methylpiperidine (131 mg, 1.14 mmol), Cu(I)I (14.5 mg, 0.0762 mmol), K2CO3 (263 mg, 1.91 mmol) and L-proline (17.6 mg, 0.152 mmol) in DMSO (6 mL) and the reaction mixture was heated at 100° C. for 12 hours. The reaction with diluted with CH2Cl2 and water (10 mL) was added. The organic layer was then washed with water (10 mL), brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (5% MeOH in CH2Cl2) to afford the product (130 mg, 66.7% yield) as a brown oil. LRMS (APCI pos) m/e 511.1 (M+H).

Workup

  1. customThe reaction
  2. additionwas added
  3. washThe organic layer was then washed with water (10 mL), brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography (5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-b385a59f6d08405ea921ff3e6cafc361
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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