Dimethylformamide → N-[[6-[1,6-dihydro-1-methyl-4-(methylamino)imidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]-2-pyridinyl]methyl]-3-methoxy-propanamide

HRID 2387704Notes

Reaction equation

HRID 2387704 reaction equation
Cl.[CH3:2][N:3]([CH3:12])[CH2:4][CH2:5][CH2:6][N:7]=[C:8]=[N:9][CH2:10]C.O[N:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]=N1.C([N:26]([CH:29](C)C)CC)(C)C.[CH3:32][O:33][CH2:34][CH2:35][C:36]([OH:38])=O.[C:39](O)([C:41](F)(F)F)=O.C[N:47](C)C=O>O.CO>[CH3:2][N:3]1[C:4]2=[C:39]3[CH:41]=[C:10]([C:18]4[N:14]=[C:22]([CH2:17][NH:16][C:36](=[O:38])[CH2:35][CH2:34][O:33][CH3:32])[CH:21]=[CH:20][CH:19]=4)[NH:9][C:8]3=[N:7][C:6]([NH:26][CH3:29])=[C:5]2[N:47]=[CH:12]1

Participants

9

Reactant 6

HCID 6228DimethylformamideHCID 6422Trifluoroacetic acid2×HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1344423-Methoxypropionic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 57393214N-[[6-[1,6-dihydro-1-methyl-4-(methylamino)imidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]-2-pyridinyl]methyl]-3-methoxy-propanamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent2×

Procedure

To a mixture of A215 (0.020 g, 0.065 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.019 g, 0.098 mmol), 1-hydroxybenzotriazole (0.013 g, 0.098 mmol), and diisopropylethylamine (0.034 mL, 0.195 mmol) in anhydrous dimethylformamide (2 mL) was added 3-methoxypropionic acid (9.20 μL, 0.098 mmol). The reaction mixture was stirred at room temperature overnight (After ˜3 hr, the reaction mixture became homogenous). The solvent was removed under reduced pressure, and the residue was diluted with dichloromethane, washed with water, and dried over anhydrous sodium sulfate. Concentration under pressure followed by purification by flash silica gel chromatography using a 5% mixture of methanol in dichloromethane afforded 0.018 g (69%) of A216 as a yellow solid. The compound had an HPLC retention time=1.84 min. (Column: Chromolith SpeedROD 4.6×50 mm−4 min.; Solvent A=10% MeOH, 90% H2O, and 0.1% TFA; Solvent B=90% MeOH, 10% H2O, and 0.1% TFA) and a LC/MS M+1=394.37. 1H NMR (400 MHz, CDCl3) δ ppm 2.62 (t, J=7.15 Hz, 2H) 3.15 (d, J=6.60 Hz, 3H) 3.54 (s, 3H) 3.78 (t, J=7.15 Hz, 2H) 4.01 (s, 3H) 4.56 (d, J=6.10 Hz, 2H) 5.49-5.54 (m, 1H) 6.96-6.98 (m, 2H) 7.51-7.58 (m, 3H) 9.98 (s, 1H)

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionthe residue was diluted with dichloromethane
  3. washwashed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationConcentration under pressure
  6. customfollowed by purification by flash silica gel chromatography
  7. customafforded 0.018 g (69%) of A216 as a yellow solid

Sources & evidence

ORD record
ord-1a61012c5e9642dfaf5be364ac3ba547
Source dataset
uspto-grants-2012_09
Patent number
US08268855B2

Reaction notes

Loading…