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

HRID 659061Notes

Reaction equation

HRID 659061 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=O)C>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 DMF (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 by LCMS, the mixture was diluted with water and extracted with EtOAc. 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 by LCMS
  4. additionthe mixture was diluted with water
  5. extractionextracted with EtOAc
  6. extractionThe organic extract
  7. customwas dried
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-2bf665f76f454953a7814639ac4b9429
Source dataset
uspto-grants-2011_12
Patent number
US08080563B2

Reaction notes

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