Sodium Carbonate → HCID 68747842, compound

HRID 1047124Notes

Reaction equation

HRID 1047124 reaction equation
C([O:8][P:9]([O:19][CH2:20][C@@H:21]([N:26]1[C:35]2[C:30](=[CH:31][C:32](Br)=[CH:33][N:34]=2)[C:29](=[O:37])[C:28]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:27]1)[CH2:22][CH:23]([CH3:25])[CH3:24])([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])C1C=CC=CC=1.[CH2:43]([NH:45][C:46](=[O:66])[NH:47][C:48]1[N:53]=[CH:52][C:51](B(O)O)=[C:50]([C:57]2[S:58][CH:59]=[C:60]([C:62]([F:65])([F:64])[F:63])[N:61]=2)[CH:49]=1)[CH3:44].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]([O:11][P:9]([O:19][CH2:20][C@@H:21]([N:26]1[C:35]2[C:30](=[CH:31][C:32]([C:51]3[CH:52]=[N:53][C:48]([NH:47][C:46](=[O:66])[NH:45][CH2:43][CH3:44])=[CH:49][C:50]=3[C:57]3[S:58][CH:59]=[C:60]([C:62]([F:65])([F:63])[F:64])[N:61]=3)=[CH:33][N:34]=2)[C:29](=[O:37])[C:28]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:27]1)[CH2:22][CH:23]([CH3:25])[CH3:24])([OH:8])=[O:10])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 594161896-(3-Ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid2×HCID 68749161HCID 68749161, compound2×

Product 1

HCID 68747842HCID 68747842, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

In a round bottomed flask ethyl 1-[(2S)-1-{[bis(benzyloxy)phosphoryl]oxy}-4-methylpentan-2-yl]-6-bromo-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 28, 700 mg, 1.05 mmol), 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 565 mg, 1.28 mmol) and aqueous 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. Tetrakis (triphenylphosphine) palladium (122 mg, 0.10 mmol) was added under argon atmosphere and the reaction mixture was heated to 80° C. for 3 h. After completion of the reaction, the reaction mixture was cooled to room temperature, filtered through celite, the filtrate was poured into water to give a solid. The solid was filtered and washed with water then dried to afford 330 mg (50%) of ethyl 1-[(2S)-1-{[(benzyloxy)(hydroxy)phosphoryl]oxy}-4-methylpentan-2-yl]-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. 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. customto give a solid
  7. filtrationThe solid was filtered
  8. washwashed with water
  9. customthen dried

Sources & evidence

ORD record
ord-009971eacf1d4451841a0386a2c6169e
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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