Sodium Carbonate → 3-Hydroxypropyl 1-ethyl-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate

HRID 1047120Notes

Reaction equation

HRID 1047120 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[N:8]([CH2:12][CH3:13])[CH:7]=[C:6]([C:14]([O:16][CH2:17][CH2:18][CH2:19][OH:20])=[O:15])[C:5]2=[O:21].[CH2:22]([NH:24][C:25](=[O:45])[NH:26][C:27]1[N:32]=[CH:31][C:30](B(O)O)=[C:29]([C:36]2[S:37][CH:38]=[C:39]([C:41]([F:44])([F:43])[F:42])[N:40]=2)[CH:28]=1)[CH3:23].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[CH2:12]([N:8]1[C:9]2[C:4](=[CH:3][C:2]([C:30]3[CH:31]=[N:32][C:27]([NH:26][C:25](=[O:45])[NH:24][CH2:22][CH3:23])=[CH:28][C:29]=3[C:36]3[S:37][CH:38]=[C:39]([C:41]([F:44])([F:42])[F:43])[N:40]=3)=[CH:11][N:10]=2)[C:5](=[O:21])[C:6]([C:14]([O:16][CH2:17][CH2:18][CH2:19][OH:20])=[O:15])=[CH:7]1)[CH3:13]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 594161896-(3-Ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid2×HCID 687508073-Hydroxypropyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate2×

Product 1

HCID 687515903-Hydroxypropyl 1-ethyl-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylateYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-Hydroxypropyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 24, 400 mg, 1.46 mmol) was dissolved in dimethylformamide (35 mL) and the solution was purged with argon. Tetrakis (triphenylphosphine) palladium (167 mg, 0.14 mM) followed by 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 775 mg, 1.75 mmol) was added and the mixture was stirred for 20 min at room temperature. Sodium carbonate solution (678 mg, 5.84 mmol) (dissolved in minimum amount of water) was added and the reaction mixture was heated to 90° C. for 3 h. The reaction mixture was passed through celite and the celite was washed with dimethylformamide. The dimethylformamide layer was poured into water (100 mL) and a precipitate formed. The precipitate was filtered and dried then purified by flash column chromatography over silica gel (100-200 mesh) using methanol (5%) in chloroform as eluent to afford 360 mg (65%) 3-hydroxypropyl 1-ethyl-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate as white solid.

Workup

  1. customthe solution was purged with argon
  2. additionwas added
  3. temperaturethe reaction mixture was heated to 90° C. for 3 h
  4. washthe celite was washed with dimethylformamide
  5. additionThe dimethylformamide layer was poured into water (100 mL)
  6. customa precipitate formed
  7. filtrationThe precipitate was filtered
  8. customdried
  9. customthen purified by flash column chromatography over silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-d8b51bfa866d4e568c51854cda92f7cd
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

Loading…