Water → HCID 57619338, compound

HRID 1754726Notes

Reaction equation

HRID 1754726 reaction equation
C(OC([N:8]1[C:12]2=[N:13][CH:14]=[CH:15][CH:16]=[C:11]2[C:10]([CH2:17][C:18]2[C:19]([F:25])=[N:20][C:21]([F:24])=[CH:22][CH:23]=2)=[CH:9]1)=O)(C)(C)C.ClC1C=CC(CN)=CC=1.C(N(CC)C(C)C)(C)C.O>CN1CCCC1=O>[F:25][C:19]1[C:18]([CH2:17][C:10]2[C:11]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[NH:8][CH:9]=2)=[CH:23][CH:22]=[C:21]([F:24])[N:20]=1

Participants

6

Reactant 4

HCID 962WaterHCID 660364-ChlorobenzylamineHCID 81531DiisopropylethylamineHCID 57619389HCID 57619389, compound

Product 1

HCID 57619338HCID 57619338, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
50 °C

Procedure

To 3-(2,6-difluoro-pyridin-3-ylmethyl)-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester (536, 0.35 g, 1.0 mmol, prepared as described in Example 49, Scheme 164, replacing 5-chloro-1H-pyrrolo[2,3-b]pyridine 532 with 1H-pyrrolo[2,3-b]pyridine in step 1) in N-methylpyrrolidinone (3.00 mL) were added p-chlorobenzylamine (0.20 mL, 1.6 mmol) and N,N-diisopropylethylamine (0.30 mL, 0.0017 mol). The reaction was stirred at 50° C. for 72 hours. The reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and the crude intermediate was dissolve in dichloromethane (15.0 mL) and trifluoroacetic acid (0.5 mL). The reaction was stirred at room temperature for 2 hours, then concentrated, poured into aqueous potassium carbonate, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 35% ethyl acetate in hexane to give a white solid (P-0154, 0.18 g, 72%). MS (ESI) [M+H+]+=246.2.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. dissolutionthe crude intermediate was dissolve in dichloromethane (15.0 mL)
  6. stirringThe reaction was stirred at room temperature for 2 hours
  7. concentrationconcentrated
  8. additionpoured into aqueous potassium carbonate
  9. extractionextracted with ethyl acetate
  10. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated
  13. custompurified by silica gel column chromatography
  14. washeluting with 35% ethyl acetate in hexane
  15. customto give a white solid (P-0154, 0.18 g, 72%)

Sources & evidence

ORD record
ord-5d5a2b68997e4fcf9ff28a3995f217a1
Source dataset
uspto-grants-2015_10
Patent number
US09169250B2

Reaction notes

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