Sodium Carbonate → Ethyl 1-cyclopropyl-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 1047113Notes

Reaction equation

HRID 1047113 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[N:8]([CH:12]1[CH2:14][CH2:13]1)[CH:7]=[C:6]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[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>[CH:12]1([N:8]2[C:9]3[C:4](=[CH:3][C:2]([C:29]4[CH:30]=[N:31][C:26]([NH:25][C:24](=[O:44])[NH:23][CH2:21][CH3:22])=[CH:27][C:28]=4[C:35]4[S:36][CH:37]=[C:38]([C:40]([F:43])([F:41])[F:42])[N:39]=4)=[CH:11][N:10]=3)[C:5](=[O:20])[C:6]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:7]2)[CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 594161896-(3-Ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid2×HCID 68750837Ethyl 6-bromo-1-cyclopropyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate2×

Product 1

HCID 68747362Ethyl 1-cyclopropyl-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 20.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

In a round bottomed flask, ethyl 6-bromo-1-cyclopropyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 16, 200 mg, 0.59 mmol), 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 367 mg, 0.83 mmol) and sodium carbonate (125 mg, 1.18 mmol) were combined and suspended in dimethylformamide (10 mL). Argon gas was purged through the above suspension for 15 min. At the end of this period, tetrakis (triphenylphosphine) palladium (68 mg, 0.05 mM) was added under argon atmosphere and the reaction mixture was heated to 40° C. for 6 h. After completion of the reaction, the reaction mixture was cooled to room temperature and filtered through celite. The filtrate was poured into water and stirred for 30 min to obtain a solid which was filtered and washed with water and dried to afford 70 mg (20%) of ethyl 1-cyclopropyl-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.

Workup

  1. customArgon gas was purged through the above suspension for 15 min
  2. additionAt the end of this period, tetrakis (triphenylphosphine) palladium (68 mg, 0.05 mM) was added under argon atmosphere
  3. customAfter completion of the reaction
  4. temperaturethe reaction mixture was cooled to room temperature
  5. filtrationfiltered through celite
  6. additionThe filtrate was poured into water
  7. customto obtain a solid which
  8. filtrationwas filtered
  9. washwashed with water
  10. customdried

Sources & evidence

ORD record
ord-ba5cb085782e424890b31ee877bd385f
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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