Isopropylamine → N-Isopropyl-5-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-nicotinamide

HRID 901363Notes

Reaction equation

HRID 901363 reaction equation
C(O[C:4](=[O:38])[C:5]1[CH:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[O:26][CH3:27])=[CH:18][N:17](S(C4C=CC(C)=CC=4)(=O)=O)[C:14]3=[N:15][CH:16]=2)[CH:8]=[N:7][CH:6]=1)C.[CH:39]([NH2:42])([CH3:41])[CH3:40]>>[CH:39]([NH:42][C:4](=[O:38])[C:5]1[CH:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[O:26][CH3:27])=[CH:18][NH:17][C:14]3=[N:15][CH:16]=2)[CH:8]=[N:7][CH:6]=1)([CH3:41])[CH3:40]

Participants

3

Reactant 2

HCID 6363IsopropylamineHCID 596999005-[3-(2-Methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]nicotinic acid ethyl ester

Product 1

HCID 59699844N-Isopropyl-5-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-nicotinamideYield 35%

Procedure

Into a 5 mL screw-cap vial were added 5-[3-(2-Methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-nicotinic acid ethyl ester (50.2 mg, 0.095 mmol) and isopropylamine (500 μL). The vial was sealed and placed in heated block at 100° C. for 48 h. The reaction solution was concentrated and the residue was dissolved in 1:1 MeOH/acetone (2 mL total) and treated with 100 μL of 50% w/w KOH(aq) for 1 h. Glacial Acetic acid was added to obtain pH 7, then the reaction mixture was concentrated. The residue was partitioned between EtOAc and water, then the layers were separated, and the organic phase was washed 2× with water. The organic phase was treated with brine, dried (Na2SO4), filtered and concentrated. Purification by flash silica gel chromatography using a gradient of ethyl acetate (containing 10% MeOH) and hexanes afforded the title compound as a white powder (13 mg, 35%). 1H-NMR (500 MHz, d6-DMSO) δ=11.96 (br. s, 1H), 9.05 (d, J=2.5 Hz, 1H), 8.94 (d, J=2.0 Hz, 1H), 8.64 (d, J=2.0 Hz, 1H), 8.51 (d, J=8.0 Hz, 1H), 8.46 (d, J=2.0 Hz, 1H), 8.30 (d, J=2.0 Hz, 1H), 7.76 (s, 1H), 7.61 (d, J=5.5 Hz, 1H), 7.29 (dd, J=2, 7.5 Hz, 1H), 7.12 (d, J=7.5 1H), 7.04 (d, J=7.5 Hz, 1H), 4.11 (m, 1H), 3.84 (s, 3H), 1.17 (s, 6H); MS: m/z 387.1 [MH+].

Workup

  1. customInto a 5 mL screw-cap vial
  2. customThe vial was sealed
  3. concentrationThe reaction solution was concentrated
  4. dissolutionthe residue was dissolved in 1:1 MeOH/acetone (2 mL total)
  5. additiontreated with 100 μL of 50% w/w KOH(aq) for 1 h
  6. additionGlacial Acetic acid was added
  7. customto obtain pH 7
  8. concentrationthe reaction mixture was concentrated
  9. customThe residue was partitioned between EtOAc and water
  10. customthe layers were separated
  11. washthe organic phase was washed 2× with water
  12. additionThe organic phase was treated with brine
  13. dry with materialdried (Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customPurification by flash silica gel chromatography

Sources & evidence

ORD record
ord-3095a09777804674bc26337928d36e14
Source dataset
uspto-grants-2008_04
Patent number
US07361763B2

Reaction notes

Loading…