Sodium Bicarbonate → 4-(3-Cyano-4-fluorophenyl)-5-(3-cyanophenyl)-1,3-thiazole-2-carboxylic acid

HRID 2038380Notes

Reaction equation

HRID 2038380 reaction equation
[C:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1)#[N:2].Br[C:13]1[S:17][C:16]([C:18]([O:20]CC)=[O:19])=[N:15][C:14]=1[C:23]1[CH:28]=[CH:27][C:26]([F:29])=[C:25]([C:30]#[N:31])[CH:24]=1.C(=O)(O)[O-].[Na+]>COCCOC.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:30]([C:25]1[CH:24]=[C:23]([C:14]2[N:15]=[C:16]([C:18]([OH:20])=[O:19])[S:17][C:13]=2[C:7]2[CH:6]=[CH:5][CH:4]=[C:3]([C:1]#[N:2])[CH:8]=2)[CH:28]=[CH:27][C:26]=1[F:29])#[N:31]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 27343253-Cyanophenylboronic acidHCID 70801513Ethyl 5-bromo-4-(3-cyano-4-fluorophenyl)-1,3-thiazole-2-carboxylate

Product 1

HCID 703148164-(3-Cyano-4-fluorophenyl)-5-(3-cyanophenyl)-1,3-thiazole-2-carboxylic acid

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

At room temperature, 217 mg (1.48 mmol) of (3-cyanophenyl)boronic acid are added to 350 mg (0.985 mmol) of the compound from Example 29A and 56.9 mg (0.049 mmol) of tetrakis(triphenylphosphine)palladium in 26 ml of DME. 252 mg (3.01 mmol) of sodium bicarbonate in 11 ml of water are subsequently added, and the mixture is stirred under reflux for 2 h. The reaction solution is subsequently concentrated under reduced pressure and the residue is taken up in ethyl acetate and washed with a saturated aqueous sodium chloride solution. The organic phase is dried over magnesium sulfate, filtered and concentrated. The residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient). 47.3 mg (14% of theory) of the title compound are obtained.

Workup

  1. temperatureunder reflux for 2 h
  2. concentrationThe reaction solution is subsequently concentrated under reduced pressure
  3. washwashed with a saturated aqueous sodium chloride solution
  4. dry with materialThe organic phase is dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient)

Sources & evidence

ORD record
ord-9cca4f2f77114b0889a022817903967a
Source dataset
uspto-grants-2013_11
Patent number
US08575357B2

Reaction notes

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