Sodium Carbonate → Ethyl 1-[2-(dimethylamino)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 1047117Notes

Reaction equation

HRID 1047117 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[N:8]([CH2:12][CH2:13][N:14]([CH3:16])[CH3:15])[CH:7]=[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:5]2=[O:22].[CH2:23]([NH:25][C:26](=[O:46])[NH:27][C:28]1[N:33]=[CH:32][C:31](B(O)O)=[C:30]([C:37]2[S:38][CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[N:41]=2)[CH:29]=1)[CH3:24].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>[CH3:15][N:14]([CH3:16])[CH2:13][CH2:12][N:8]1[C:9]2[C:4](=[CH:3][C:2]([C:31]3[CH:32]=[N:33][C:28]([NH:27][C:26](=[O:46])[NH:25][CH2:23][CH3:24])=[CH:29][C:30]=3[C:37]3[S:38][CH:39]=[C:40]([C:42]([F:45])([F:43])[F:44])[N:41]=3)=[CH:11][N:10]=2)[C:5](=[O:22])[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:7]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 594161896-(3-Ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid2×HCID 68747522Ethyl 6-bromo-1-[2-(dimethylamino)ethyl]-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate2×

Product 1

HCID 68748480Ethyl 1-[2-(dimethylamino)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 33.7%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

In a round bottomed flask ethyl 6-bromo-1-[2-(dimethylamino)ethyl]-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 21, 200 mg, 0.54 mmol), 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 288 mg, 0.65 mmol) and sodium carbonate (115 mg, 1.08 mmol) were combined and suspended in dimethylformamide (10 mL) and purged with argon gas for 10 min. Tetrakis (triphenylphosphine) palladium (62 mg, 0.05 mmol) was added under argon atmosphere and the reaction mixture was heated to 90° C. for 2 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 was stirred for 20 min. The obtained solid was filtered and washed with water then dried to afford 110 mg (33%) of ethyl 1-[2-(dimethylamino)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.

Workup

  1. custompurged with argon gas for 10 min
  2. customAfter completion of the reaction
  3. temperaturethe reaction mixture was cooled to room temperature
  4. filtrationfiltered through celite
  5. additionThe filtrate was poured into water
  6. filtrationThe obtained solid was filtered
  7. washwashed with water
  8. customthen dried

Sources & evidence

ORD record
ord-0f7f89897cde4d0a836872d4aac1f1b3
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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