Sodium Iodide → HCID 57731459, compound

HRID 2234639Notes

Reaction equation

HRID 2234639 reaction equation
[F:1][C:2]1[C:3]([NH:40]C(=O)C(F)(F)F)=[C:4]([CH:10]=[C:11]([C:13]2[CH:14]=[C:15]3[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[O:28][CH3:29])=[CH:20][N:19](S(C4C=CC(C)=CC=4)(=O)=O)[C:16]3=[N:17][CH:18]=2)[CH:12]=1)[C:5]([N:7]([CH3:9])[CH3:8])=[O:6].Br[CH2:48][C:49]([NH:51][CH:52]([CH3:54])[CH3:53])=[O:50].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CN(C)C=O>[F:1][C:2]1[C:3]([NH:40][CH2:48][C:49](=[O:50])[NH:51][CH:52]([CH3:54])[CH3:53])=[C:4]([CH:10]=[C:11]([C:13]2[CH:14]=[C:15]3[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[O:28][CH3:29])=[CH:20][NH:19][C:16]3=[N:17][CH:18]=2)[CH:12]=1)[C:5]([N:7]([CH3:9])[CH3:8])=[O:6]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium Carbonate2×HCID 125092612-Bromo-N-isopropylacetamide2×HCID 57731522HCID 57731522, compound

Product 1

HCID 57731459HCID 57731459, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a scintillation vial was combined 40 mg (0.06 mmol) of 3-fluoro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-2-(2,2,2-trifluoro-acetylamino)-benzamide, 165 mg (0.092 mmol) of 2-bromo-N-isopropyl-acetamide, 17 mg (0.12 mmol) of potassium carbonate, and 0.5 mL N,N-dimethylformamide. The vial was heated in a heating block at 60° C. for 19 hours. 5.5 mg (0.03 mmol) 2-bromo-N-isopropyl-acetamide and 8.5 mg (0.06 mmol) potassium carbonate were added. Additionally, 9.0 mg (0.06 mmol) of sodium iodide was added and the reaction was heated to 60° C. for another 72 hours. The reaction was allowed to cool to room temperature and salts were filtered off. The crude filtrate was diluted with 0.5 mL methanol and 150 μL of a 50% w/v potassium hydroxide aqueous solution was added. The reaction was stirred 1 hour at room temperature. The solution was neutralized by adding acetic acid dropwise and then the reaction was concentrated to dryness. The resulting residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate (containing 10% methanol) and hexanes. The clean fractions were concentrated and then lyophilized overnight to afford 13.3 mg (0.003 mmol, 43% yield) of 3-fluoro-2-[(isopropylcarbamoyl-methyl)-amino]-5-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide as a pale yellow powder. 1H NMR (500 MHz, CD3OD) δ 8.42 (s, br., 1H), 8.18 (d, 1H), 7.65 (s, 1H), 7.58 (dd, 1H), 7.45 (dd, 1H), 7.31 (t, 1H), 7.25 (d, 1H), 7.13 (d, 1H), 7.06 (t, 1H), 4.02 (m, 1H), 3.85 (s, 3H), 3.84 (s, 2H), 3.15 (s, br., 3H), 3.04 (s, br., 3H), 1.16 (d, 6H); MS: m/z 504.1 (M+H+).

Workup

  1. temperaturethe reaction was heated to 60° C. for another 72 hours
  2. temperatureto cool to room temperature
  3. filtrationsalts were filtered off
  4. additionThe crude filtrate was diluted with 0.5 mL methanol and 150 μL of a 50% w/v potassium hydroxide aqueous solution
  5. additionwas added
  6. additionby adding acetic acid dropwise
  7. concentrationthe reaction was concentrated to dryness
  8. customThe resulting residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate (containing 10% methanol) and hexanes
  9. concentrationThe clean fractions were concentrated
  10. waitlyophilized overnight

Sources & evidence

ORD record
ord-c97a0388fdcc42bf9913bad051e19392
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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