Cesium carbonate → Ethyl 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 1047112Notes

Reaction equation

HRID 1047112 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][CH3:18])=[O:15])[C:5]2=[O:19].[CH2:20]([NH:22][C:23](=[O:43])[NH:24][C:25]1[N:30]=[CH:29][C:28](B(O)O)=[C:27]([C:34]2[S:35][CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[N:38]=2)[CH:26]=1)[CH3:21].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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:28]3[CH:29]=[N:30][C:25]([NH:24][C:23](=[O:43])[NH:22][CH2:20][CH3:21])=[CH:26][C:27]=3[C:34]3[S:35][CH:36]=[C:37]([C:39]([F:42])([F:40])[F:41])[N:38]=3)=[CH:11][N:10]=2)[C:5](=[O:19])[C:6]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:7]1)[CH3:13]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 594161896-(3-Ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid2×HCID 68748009Ethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate2×

Product 1

HCID 68747705Ethyl 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 25%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
85 °C

Procedure

In a round bottomed flask, ethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 15, 400 mg, 1.3 mmol), 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 700 mg, 1.72 mmol) and cesium carbonate (3.78 g, 2.46 mmol) were combined and suspended in 10 mL of dioxane:water (8:2). The suspension was purged with argon for 15 min. then tetrakis (triphenylphosphine) palladium (140 mg, 0.2 mmol) was added under argon atmosphere and the reaction mixture was heated to 80-90° C. for 5 h. After completion of the reaction, the reaction mixture was cooled to room temperature and filtered through celite. The filtrate was concentrated under reduced pressure to a residue, to which acetonitrile was added. The precipitated solid was filtered and dried to afford 150 mg (25%) of ethyl 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.

Workup

  1. customThe suspension was purged with argon for 15 min.
  2. customAfter completion of the reaction
  3. temperaturethe reaction mixture was cooled to room temperature
  4. filtrationfiltered through celite
  5. concentrationThe filtrate was concentrated under reduced pressure to a residue, to which acetonitrile
  6. additionwas added
  7. filtrationThe precipitated solid was filtered
  8. customdried

Sources & evidence

ORD record
ord-b37a76790c104171ba89297c5c90c0b9
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

Loading…