4-Methoxybenzylamine → HCID 178509959, compound

HRID 1157422Notes

Reaction equation

HRID 1157422 reaction equation
C(OC([N:8]1[C:12]2=[N:13][C:14](F)=[CH:15][CH:16]=[C:11]2[C:10]([CH2:18][O:19][C:20]2[CH:25]=[C:24]([F:26])[C:23]([Cl:27])=[C:22]([O:28][C:29]3[CH:34]=[C:33]([C:35]#[N:36])[CH:32]=[C:31]([Cl:37])[CH:30]=3)[CH:21]=2)=[N:9]1)=O)(C)(C)C.COC1C=CC(C[NH2:45])=CC=1>CN1C(=O)CCC1.CCOC(C)=O.C(O)(C(F)(F)F)=O>[NH2:45][C:14]1[N:13]=[C:12]2[NH:8][N:9]=[C:10]([CH2:18][O:19][C:20]3[CH:25]=[C:24]([F:26])[C:23]([Cl:27])=[C:22]([CH:21]=3)[O:28][C:29]3[CH:34]=[C:33]([CH:32]=[C:31]([Cl:37])[CH:30]=3)[C:35]#[N:36])[C:11]2=[CH:16][CH:15]=1

Participants

6

Reactant 2

HCID 754524-MethoxybenzylamineHCID 44549123tert-butyl3-{[4-chloro-3-(3-chloro-5-cyanophenoxy)-5-fluorophenoxy]methyl}-6-fluoro-1H-pyrazolo[3,4-b]pyridine-1-carboxylate

Product 1

HCID 178509959HCID 178509959, compoundYield 4.3%

Reagents, catalysts & solvents 3

HCID 6422Trifluoroacetic acidSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
95 °C

Procedure

Under a nitrogen atmosphere, tert-butyl3-{[4-chloro-3-(3-chloro-5-cyanophenoxy)-5-fluorophenoxy]methyl}-6-fluoro-1H-pyrazolo[3,4-b]pyridine-1-carboxylate (50-6) (230 mg, 0.420 mmol) was dissolved in NMP (4 mL, 0.1 M). Next, 4-methoxybenzylamine (288 mg, 2.101 mmol) was added and the reaction was heated to 95° C. for 2 hours. It was then diluted with EtOAc (4 mL). It was partitioned with water (3 mL) and then extracted with EtOAc (3×4 mL). The organic extracts were then washed with water (3×4 mL) and brine (1×4 mL), dried over sodium sulfate and concentrated. The crude reaction material was then diluted with TFA (3 mL) and heated to 65° C. for 2 hours. It was then concentrated and purified on a reverse phase system (5%-95% AcCN/H2O with 0.5% TFA) to give 3-{5-[(6-amino-1H-pyrazolo[3,4-b]pyridin-3-yl)methoxy]-2-chloro-3-fluorophenoxy}-5-chlorobenzonitrile (50-7) (8 mg, 4%). LCMS (ES) m/z 445.9 (M+).

Workup

  1. customIt was partitioned with water (3 mL)
  2. extractionextracted with EtOAc (3×4 mL)
  3. washThe organic extracts were then washed with water (3×4 mL) and brine (1×4 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude reaction material
  7. temperatureheated to 65° C. for 2 hours
  8. concentrationIt was then concentrated
  9. custompurified on a reverse phase system (5%-95% AcCN/H2O with 0.5% TFA)

Sources & evidence

ORD record
ord-1eeaf7d8316c4b92a73e716876603550
Source dataset
uspto-grants-2010_10
Patent number
US07807684B2

Reaction notes

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