Acetic Acid → {2-amino-3-chloro-5-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-morpholin-4-yl-methanone

HRID 2234629Notes

Reaction equation

HRID 2234629 reaction equation
[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:8]([C:12]2[CH:13]=[C:14]3[C:20]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[O:27][CH3:28])=[CH:19][N:18](S(C4C=CC(C)=CC=4)(=O)=O)[C:15]3=[N:16][CH:17]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.[OH-].[K+].C(O)(=O)C>CN(C)C=O.CO>[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:8]([C:12]2[CH:13]=[C:14]3[C:20]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[O:27][CH3:28])=[CH:19][NH:18][C:15]3=[N:16][CH:17]=2)=[CH:7][C:3]=1[C:4]([N:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1)=[O:6]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8083MorpholineHCID 14797Potassium HydroxideHCID 577314272-amino-3-chloro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-benzoic acid

Product 1

HCID 59700220{2-amino-3-chloro-5-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-morpholin-4-yl-methanoneYield 32.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

25.0 mg (0.046 mmol) of 2-amino-3-chloro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-benzoic acid was combined with 18.5 mg (0.114 mmol) of N,N′-carbonyldiimidazole in 1.0 mL dimethylformamide. The solution was stirred at room temperature for 2 hours whereupon 9.9 μL (0.114 mmol) of morpholine was added and the solution was stirred at room temperature for 16 hours. The crude reaction mixture was then diluted with 1.0 mL methanol and 100 μL of 50% w/v potassium hydroxide aqueous solution was added. The mixture was stirred at room temperature for 2 hours and then neutralized with acetic acid. The material was filtered through a 0.45 μm syringe filter and purified by mass-triggered reverse phase HPLC in a gradient of acetonitrile and water (containing 0.1% formic acid). The clean fractions were lyophilized to afford 6.9 mg (0.015 mmol, 32% yield) of {2-amino-3-chloro-5-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-morpholin-4-yl-methanone as a fluffy white powder. 1H NMR (500 MHz, MeOD) δ 8.39 (d, 1H), 8.15 (d, 1H), 7.65 (s, 1H), 7.64 (d, 1H), 7.58 (dd, 1H), 7.36 (d, 1H), 7.31 (t, 1H), 7.13 (d, 1H), 7.06 (t, 1H), 3.86 (s, 3H), 3.72 (s, br., 8H); MS: m/z 463.0 (M+H+).

Workup

  1. additionwas added
  2. customThe crude reaction mixture
  3. additionwas added
  4. stirringThe mixture was stirred at room temperature for 2 hours
  5. filtrationThe material was filtered through a 0.45 μm syringe
  6. filtrationfilter
  7. custompurified by mass-triggered reverse phase HPLC in a gradient of acetonitrile and water (containing 0.1% formic acid)

Sources & evidence

ORD record
ord-11d8c29eb4334c11ae6d2b538f44b18a
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

Loading…