Sodium Carbonate → HCID 131734893, compound

HRID 920826Notes

Reaction equation

HRID 920826 reaction equation
[C:1]([C:4]1[C:5](I)=[N:6][N:7]2[CH2:12][CH:11]([C:13]([F:16])([F:15])[F:14])[N:10]([C:17]([O:19]C(C)(C)C)=[O:18])[CH2:9][C:8]=12)(=[O:3])[NH2:2].[Cl:25][C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][C:31]=1[F:32].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([C:4]1[C:5]([C:28]2[CH:29]=[CH:30][C:31]([F:32])=[C:26]([Cl:25])[CH:27]=2)=[N:6][N:7]2[CH2:12][CH:11]([C:13]([F:15])([F:14])[F:16])[N:10]([C:17]([O:19][CH2:1][CH2:4][CH2:8][CH3:9])=[O:18])[CH2:9][C:8]=12)(=[O:3])[NH2:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 118071315HCID 118071315, compound

Product 1

HCID 131734893HCID 131734893, compoundYield 142%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of Intermediate 346F (0.35 g, 0.761 mmol) and (3-chloro-4-fluorophenyl)boronic acid (0.215 g, 0.837 mmol) in DMF (2 mL) was added a solution of Na2CO3 (0.242 g, 2.282 mmol) in water (1 mL) and the reaction mixture was purged with nitrogen for 5 min. Pd(PPh3)4 (0.044 g, 0.038 mmol) was then added and the reaction mixture was stirred at 100° C. for 18 h. The reaction mixture was cooled to RT and extracted with EtOAc (2×50 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered and the filtrate concentrated under reduced pressure. The crude compound was purified by silica gel chromatography (12 g REDISEP® column, eluting with 5% MeOH in CHCl3). Fractions containing the product were combined and evaporated to afford Intermediate 346G as a white solid (0.25 g, 68%). MS(ES): m/z=464.5 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.92-7.82 (m, 1H), 7.73-7.67 (m, 1H), 7.65-7.52 (m, 1H), 7.51-7.44 (m, 1H), 7.41-7.21 (m, 2H), 5.17-5.05 (m, 1H), 4.65-4.48 (m, 3H), 1.50 (s, 9H).

Workup

  1. customthe reaction mixture was purged with nitrogen for 5 min
  2. temperatureThe reaction mixture was cooled to RT
  3. extractionextracted with EtOAc (2×50 mL)
  4. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customThe crude compound was purified by silica gel chromatography (12 g REDISEP® column, eluting with 5% MeOH in CHCl3)
  8. additionFractions containing the product
  9. customevaporated

Sources & evidence

ORD record
ord-8ed75c1c13af416986e8d08de860f525
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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