Potassium Carbonate → HCID 68746480, compound

HRID 1047171Notes

Reaction equation

HRID 1047171 reaction equation
[F:1][C:2]1[N:11]=[C:10]2[C:5]([C:6](=[O:24])[C:7]([C:19]([O:21]CC)=[O:20])=[CH:8][N:9]2[C@@H:12]([C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:13][OH:14])=[CH:4][C:3]=1I.[CH2:26]([NH:28][C:29](=[O:49])[NH:30][C:31]1[N:36]=[CH:35][C:34](B(O)O)=[C:33]([C:40]2[S:41][CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[N:44]=2)[CH:32]=1)[CH3:27].C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[CH2:26]([NH:28][C:29](=[O:49])[NH:30][C:31]1[N:36]=[CH:35][C:34]([C:3]2[CH:4]=[C:5]3[C:10](=[N:11][C:2]=2[F:1])[N:9]([C@@H:12]([C:15]([CH3:18])([CH3:16])[CH3:17])[CH2:13][OH:14])[CH:8]=[C:7]([C:19]([OH:21])=[O:20])[C:6]3=[O:24])=[C:33]([C:40]2[S:41][CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[N:44]=2)[CH:32]=1)[CH3:27]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 594161896-(3-Ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid2×HCID 69621312HCID 69621312, compound

Product 1

HCID 68746480HCID 68746480, compound

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 12976736Bis(ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane);iron(2+)CatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of palladium (II) acetate (0.163 g, 0.72 mmol, 0.1 equiv.) and 1,1′-bis(di-tert-butylphosphino)ferrocene (0.344 g, 0.72 mmol, 0.1 equiv.) in acetonitrile (27 mL) was added (S)-ethyl 7-fluoro-1-(1-hydroxy-3,3-dimethylbutan-2-yl)-6-iodo-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate Intermediate 78 (3.35 g, 7.25 mmol, 1 equiv.) and 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazole-2-yl)pyridine-3-ylboronic acid Intermediate 9 (2.64 g, 7.32 mmol, 1.01 equiv.) and a solution of potassium carbonate (1.5 g, 10.87 mmol, 1.5 equiv.) in water (9 mL). This was stirred at 80° C. for 2 h. The reaction was cooled to room temperature and diluted with water. The precipitate was washed with water and dried. The compound was purified via silica gel chromatography and concentrated to afford (S)-6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-7-fluoro-1-(1-hydroxy-3,3-dimethylbutan-2-yl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid Intermediate 76 (1.2 g, 25%). Calcd for C29H30F4N6O5S [M+H]+: 651.2.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. washThe precipitate was washed with water
  3. customdried
  4. customThe compound was purified via silica gel chromatography
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-a3983fe0a58145ca81cb168fb1be5c08
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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