Dimethylformamide → 3-bromo-8-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one

HRID 1095770Notes

Reaction equation

HRID 1095770 reaction equation
[Br:1]N1C(=O)CCC1=O.[CH:9]1([O:14][C:15]2[C:16]([O:35][CH3:36])=[CH:17][CH:18]=[C:19]3[C:24]=2[NH:23][C:22](=[O:25])[CH:21]=[C:20]3[NH:26][C:27]2[C:32]([Cl:33])=[CH:31][N:30]=[CH:29][C:28]=2[Cl:34])[CH2:13][CH2:12][CH2:11][CH2:10]1.CN(C)C=O>O>[Br:1][C:21]1[C:22](=[O:25])[NH:23][C:24]2[C:19]([C:20]=1[NH:26][C:27]1[C:32]([Cl:33])=[CH:31][N:30]=[CH:29][C:28]=1[Cl:34])=[CH:18][CH:17]=[C:16]([O:35][CH3:36])[C:15]=2[O:14][CH:9]1[CH2:10][CH2:11][CH2:12][CH2:13]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 67184N-bromobutanimideHCID 248519098-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one

Product 1

HCID 248519123-bromo-8-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

N-Bromosuccinimide (0.104 g, 0.585 mmol) was added to a solution of 4-(3,5, -dichloropyridin-4-ylamino)-8-(cyclopentyloxy)-7-methoxyquinolin-2(1H)-one (0.246 g, 0.585 mmol, Example 1) and anhydrous dimethylformamide (3 mL) at 0° C. After 4 h at 0° C., the mixture was poured into water, and the precipitate was filtered. Saturated sodium thiosulfate solution (1 mL) was added to a solution of the filter cake and methanol (5 mL). After the dibromo intermediate was consumed, as monitored by LCMS, the mixture was diluted with water and extracted with ethyl acetate. The organic extract was dried, filtered, and concentrated to give 3-bromo-8-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one: 1H NMR (400 MHz, DMSO-d6): δ 10.56 (s, 1H), 8.88 (br s, 1H), 8.42 (s, 2H), 7.62 (d, 1H), 7.04 (d, 1H), 4.98 (m, 1H), 3.89 (s, 3H), 1.84-1.51 (m, 8H); MS (ESI): 497.8.

Workup

  1. filtrationthe precipitate was filtered
  2. additionSaturated sodium thiosulfate solution (1 mL) was added to a solution of the filter cake and methanol (5 mL)
  3. customAfter the dibromo intermediate was consumed
  4. additionthe mixture was diluted with water
  5. extractionextracted with ethyl acetate
  6. extractionThe organic extract
  7. customwas dried
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-d6bf534bb49e45c68b876b36beb79d19
Source dataset
uspto-grants-2012_03
Patent number
US08138205B2

Reaction notes

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