Hydrochloric Acid → HCID 11524694, compound

A solution of methyl 1-(4-fluorobenzyl)-3-formyl-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (312 mg, 1.0 mmol, 1.0 eq) in 4 mL anhydrous dichloromethane) was mixed with a solution of 3-methylpiperazin-2-one (114 mg, 1.0 mmol, 1.0 eq) in 4 mL dichloromethane. After the reaction mixture was stirred for 1 h at room temp., sodium triacetoxyborohydride (530 mg, 2.5 mmol, 2.5 eq.) was added, and the resulting mixture was stirred at room temp. overnight. The solvent was removed under reduced pressure, and the residue was dissolved in 8 mL of a 6:3:1 (v/v) mixture of ethylacetate/dichloromethane/methanol. The organic phase was washed with 8 mL of 1.0 M aqueous potassium carbonate, and the aqueous layer was extracted with the 6:3:1 mixture of ethylacetate/dichloromethane/methanol (2×8 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure. The residue was dissolved in 4 mL methanol. Then 1 mL 3.0 M LiOH (3.0 eq) solution was added. After the solution was stirred at rt for 3 h, 3 mL 1.0 M HCl (3.0 eq) was added, and the mixture was stirred for another 15 min. Then the solvent and excess HCl were removed under reduced pressure. The residue was dissolved in 4 mL DMF, and N-methylhydroxyamine (4 mL, 0.25 M in DMF, 1.0 eq), HATU (4 mL, 0.25 M in DMF, 1.0 eq), and triethylamine (0.42 mL, neat, 3 eq) were added. The reaction mixture was stirred at 60° C. for 16 h. The solvent was removed under reduced pressure, and the residue was subjected to prep HPLC for purification to afford the title compound (66 mg, 24% overall yield). 1HNMR (300 MHz, MeOH-d4) δ ppm: 9.08 (s, 1H), 8.85 (b, 1H), 8.32 (s, 1H), 7.37-7.25 (m, 2H), 7.08-6.96 (m, 2H), 5.62 (s, 2H), 4.75 (d, 1H), 4.47 (d, 1H), 3.90-3.77 (m, 1H), 3.54-3.32 (m, 2H), 3.35 (s, 3H), 3.25-3.12 (m, 2H), 1.65 (d, 3H). HRMS calcd for C22H25N5O3F (M+H+) 426.1941, found 426.1947. HPLC: >99% purity.

1. stirringthe resulting mixture was stirred at room temp. overnight
2. customThe solvent was removed under reduced pressure
3. dissolutionthe residue was dissolved in 8 mL of a 6:3:1 (v/v) mixture of ethylacetate/dichloromethane/methanol
4. washThe organic phase was washed with 8 mL of 1.0 M aqueous potassium carbonate
5. extractionthe aqueous layer was extracted with the 6:3:1 mixture of ethylacetate/dichloromethane/methanol (2×8 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated to dryness under reduced pressure
8. dissolutionThe residue was dissolved in 4 mL methanol
9. stirringAfter the solution was stirred at rt for 3 h
10. stirringthe mixture was stirred for another 15 min
11. customThen the solvent and excess HCl were removed under reduced pressure
12. dissolutionThe residue was dissolved in 4 mL DMF
13. stirringThe reaction mixture was stirred at 60° C. for 16 h
14. customThe solvent was removed under reduced pressure
15. customfor purification

ORD record

ord-5cf22b33abe94adc8c1fa3ebf3f30e53

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07468375B2