18-Crown-6 → HCID 68512167, compound

HRID 2241340Notes

Reaction equation

HRID 2241340 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=4[F:25])=[C:11]3[C:10](I)=[N:9]2)=[CH:5][CH:4]=1.[CH3:29][N:30]([CH3:36])[C@@H:31]1[CH2:35][CH2:34][NH:33][CH2:32]1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+].C1OCCOCCOCCOCCOCCOC1>C1COCC1.ClCCl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[NH2:24][C:21]1[CH:22]=[CH:23][C:18]([O:17][C:16]2[CH:15]=[CH:14][N:13]=[C:12]3[N:8]([CH2:7][C:6]4[CH:27]=[CH:28][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[N:9]=[C:10]([N:33]4[CH2:34][CH2:35][C@@H:31]([N:30]([CH3:36])[CH3:29])[CH2:32]4)[C:11]=23)=[C:19]([F:25])[CH:20]=1

Participants

9

Reactant 5

HCID 2855718-Crown-6HCID 634876Binap, (A+-)-HCID 2758521(3R)-(+)-3-(Dimethylamino)pyrrolidineHCID 23676156Sodium t-butoxideHCID 672210033-Fluoro-4-((3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)oxy)aniline

Product 1

HCID 68512167HCID 68512167, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred suspension of 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (49 mg, 0.1 mmol) (prepared according to Example 7, step B) and (R)—N,N-dimethylpyrrolidin-3-amine (23 mg, 0.2 mmol) in 300 μL THF at ambient temperature in a capped reaction vial was added racemic Binap (9 mg, 0.015 mmol) followed by NaOtBu (14 mg, 0.15 mmol) and 18-crown-6 (40 mg, 0.1499 mmol). The reaction purged with nitrogen gas and then held under a balloon of nitrogen. Pd(dba)2 (6 mg, 0.01 mmol) was then added and the reaction was sealed and heated to 40° C. After stirring for 72 hours, the reaction was cooled to ambient temperature, diluted to 30 mL with dichloromethane and washed with 10% sodium carbonate solution. The organics were dried (MgSO4), filtered and concentrated. The brown residue was dissolved in a minimum of dichloromethane and loaded onto a Biotage 12S column. The column was eluted with 95/5 dichloromethane/MeOH to provide the product as a tan foam (40 mg, 84%).

Workup

  1. customin a capped reaction
  2. customThe reaction purged with nitrogen gas
  3. customthe reaction was sealed
  4. temperaturethe reaction was cooled to ambient temperature
  5. washwashed with 10% sodium carbonate solution
  6. dry with materialThe organics were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe brown residue was dissolved in a minimum of dichloromethane
  10. washThe column was eluted with 95/5 dichloromethane/MeOH

Sources & evidence

ORD record
ord-5bb5f1db1d384e2a9f97d14ef3bf1ad9
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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