Sodium Carbonate → 2-{[Bis(benzyloxy)phosphoryl]oxy}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 1047121Notes

Reaction equation

HRID 1047121 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][O:19][P:20]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21])=[O:15])[C:5]2=[O:38].[CH2:39]([NH:41][C:42](=[O:62])[NH:43][C:44]1[N:49]=[CH:48][C:47](B(O)O)=[C:46]([C:53]2[S:54][CH:55]=[C:56]([C:58]([F:61])([F:60])[F:59])[N:57]=2)[CH:45]=1)[CH3:40].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:47]3[CH:48]=[N:49][C:44]([NH:43][C:42](=[O:62])[NH:41][CH2:39][CH3:40])=[CH:45][C:46]=3[C:53]3[S:54][CH:55]=[C:56]([C:58]([F:61])([F:59])[F:60])[N:57]=3)=[CH:11][N:10]=2)[C:5](=[O:38])[C:6]([C:14]([O:16][CH2:17][CH2:18][O:19][P:20]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)([O:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[O:21])=[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 687488382-{[Bis(benzyloxy)phosphoryl]oxy}ethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate2×

Product 1

HCID 687481932-{[Bis(benzyloxy)phosphoryl]oxy}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-carboxylateYield 63%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

2-{[Bis(benzyloxy)phosphoryl]oxy}ethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 25, 80 mg, 0.133 mmol) was dissolved in dimethylformamide (15 mL), and the solution was purged with argon. Tetrakis (triphenylphosphine) palladium (15 mg, 0.013 mmol) and 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 71 mg, 0.16 mmol) were added and the mixture was stirred for 20 min at room temperature. Sodium carbonate solution (57 mg, 0.53 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 solid was filtered and dried then purified by flash column chromatography over silica gel (0-8% MeOH/CHCl3) to afford 70 mg (63%) of 2-{[bis(benzyloxy)phosphoryl]oxy}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 as white solid.

Workup

  1. customthe solution was purged with argon
  2. temperaturethe reaction 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 precipitate formed
  6. filtrationThe solid was filtered
  7. customdried
  8. customthen purified by flash column chromatography over silica gel (0-8% MeOH/CHCl3)

Sources & evidence

ORD record
ord-611a45d3276645dc96f88f0e5c917e37
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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