Sodium Carbonate → 2-Hydroxyethyl 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 1047119Notes

Reaction equation

HRID 1047119 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][OH:19])=[O:15])[C:5]2=[O:20].[CH2:21]([NH:23][C:24](=[O:44])[NH:25][C:26]1[N:31]=[CH:30][C:29](B(O)O)=[C:28]([C:35]2[S:36][CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[N:39]=2)[CH:27]=1)[CH3:22].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:12]([N:8]1[C:9]2[C:4](=[CH:3][C:2]([C:29]3[CH:30]=[N:31][C:26]([NH:25][C:24](=[O:44])[NH:23][CH2:21][CH3:22])=[CH:27][C:28]=3[C:35]3[S:36][CH:37]=[C:38]([C:40]([F:43])([F:41])[F:42])[N:39]=3)=[CH:11][N:10]=2)[C:5](=[O:20])[C:6]([C:14]([O:16][CH2:17][CH2:18][OH:19])=[O:15])=[CH:7]1)[CH3:13]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 594161896-(3-Ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid2×HCID 687468242-Hydroxyethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate2×

Product 1

HCID 687508202-Hydroxyethyl 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 60%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

2-Hydroxyethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 23, 170 mg, 0.50 mmol) was dissolved in dimethylformamide (25 mL), purged with argon, tetrakis (triphenylphosphine) palladium (57 mg, 0.049 mmol) followed by 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 264 mg, 0.598 mmol) was added and stirred for 20 min at room temperature, sodium carbonate solution (231 mg, 2 mmol) (dissolved in minimum amount of water) was added to reaction mixture and the mixture was heated to 90° C. for 3 h. The reaction mixture was passed through a celite bed and the celite was washed with dimethylformamide. The dimethylformamide layer was poured into water (100 mL) and a solid precipitate formed. The solid was filtered and dried then purified by flash column chromatography over silica gel (100-200 mesh) using MeOH (0-6%) in CHCl3 as an eluent to afford 168 mg (60%) 2-hydroxyethyl 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. additionwas added
  2. temperaturethe mixture was heated to 90° C. for 3 h
  3. washthe celite was washed with dimethylformamide
  4. additionThe dimethylformamide layer was poured into water (100 mL)
  5. customa solid precipitate formed
  6. filtrationThe solid was filtered
  7. customdried
  8. customthen purified by flash column chromatography over silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-b8691f98053f472b92aa3b29debe8ff1
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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