Hydrochloric Acid → HCID 57618264, compound

HRID 1874000Notes

Reaction equation

HRID 1874000 reaction equation
[B:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[C:6]([F:13])[CH:5]=1)([OH:3])[OH:2].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.Cl.[F:48][C:49]1([F:54])[CH2:53][CH2:52][NH:51][CH2:50]1.Cl>CN(C=O)C.O>[F:48][C:49]1([F:54])[CH2:53][CH2:52][N:51]([C:8]([C:7]2[CH:11]=[CH:12][C:4]([B:1]([OH:2])[OH:3])=[CH:5][C:6]=2[F:13])=[O:10])[CH2:50]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27632014-Carboxy-3-fluorophenylboronic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 249034823,3-Difluoropyrrolidine hydrochloride

Product 1

HCID 57618264HCID 57618264, compoundYield 52.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-borono-2-fluorobenzoic acid (1.00 g, 5.44 mmol), N,N-diisopropylethylamine (2.85 mL, 16.31 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (2.163 g, 5.69 mmol) and 3,3-difluoropyrrolidine hydrochloride (1.00 g, 6.97 mmol) in DMF (6 mL) was stirred at room temperature for 22 h. Following addition of 1 N HCl (16 mL), the mixture was extracted with ethyl acetate (40 mL). HPLC analysis showed that the aqueous phase still contained product. The aqueous phase was neutralized to pH 7 with solid NaOH and K2CO3 and extracted with ethyl acetate. The combined extracts were dried (MgSO4) and concentrated to give a thick brown oil. This residue was treated with equal volume of water. The white crystalline solid formed from the mixture was collected by filtration and washed with small amount of ether to give the desired product (0.7811 g). The filtrate was purified by reverse phase HPLC (Sunfire S10 30×250 mm column, 30-50% solvent B gradient) to give additional product (0.5632 g). The combined yield of the product was 1.344 g (91% yield). MS (ES+) m/z: 274 (M+H); LC retention time: 2.68 min (analytical HPLC Method A).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (40 mL)
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined extracts were dried (MgSO4)
  4. concentrationconcentrated
  5. customto give a thick brown oil
  6. customThe white crystalline solid formed from the mixture
  7. filtrationwas collected by filtration
  8. washwashed with small amount of ether

Sources & evidence

ORD record
ord-a77ad82a466e480ab80ab7038f3d8b56
Source dataset
uspto-grants-2012_11
Patent number
US08304539B2

Reaction notes

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