Boron Trichloride → HCID 118497144, compound

HRID 522100Notes

Reaction equation

HRID 522100 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]([N:15]2[C:19]([NH:20][C:21](=[O:36])[C:22]3[CH:27]=[C:26]([C:28]4[C:33]([F:34])=[CH:32][CH:31]=[CH:30][N:29]=4)[CH:25]=[CH:24][C:23]=3[Cl:35])=[CH:18][C:17]([C:37](O)=[O:38])=[N:16]2)[CH:12]=[CH:13][CH:14]=1)C1C=CC=CC=1.[CH:40]1([NH2:43])[CH2:42][CH2:41]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.B(Cl)(Cl)Cl>CN(C=O)C.O>[Cl:35][C:23]1[CH:24]=[CH:25][C:26]([C:28]2[C:33]([F:34])=[CH:32][CH:31]=[CH:30][N:29]=2)=[CH:27][C:22]=1[C:21]([NH:20][C:19]1[N:15]([C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([OH:8])[CH:10]=2)[N:16]=[C:17]([C:37]([NH:43][CH:40]2[CH2:42][CH2:41]2)=[O:38])[CH:18]=1)=[O:36]

Participants

8

Reactant 5

HCID 25135Boron TrichlorideHCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118497189HCID 118497189, compound

Product 1

HCID 118497144HCID 118497144, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(3-(benzyloxy)phenyl)-5-(2-chloro-5-(3-fluoropyridin-2-yl)benzamido)-1H-pyrazole-3-carboxylic acid (Example 104, 220 mg, 0.373 mmol) in DMF (5 mL) was added cyclopropylamine (26 mg, 0.448 mmol) and DIPEA (241 mg, 1.87 mmol, 0.325 mL) followed by HATU (213 mg, 0.560 mmol). The reaction was stirred at room temperature for 30 minutes. The reaction was diluted with water (70 mL) and extracted with 2-MeTHF (50 mL). The organic layer was washed with brine (50 mL) dried over sodium sulphate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 20-25% EtOAc in DCM and the residue was dissolved in DCM (5 mL). Boron trichloride (1M in DCM, 1.72 mL, 1.72 mmol) was added at 0° C. and the reaction was stirred at this temperature for 40 minutes. The reaction was quenched by the addition of MeOH (1 mL) and stirred for 20 minutes. The reaction was concentrated in vacuo and purified using silica gel column chromatography eluting with 2-6% MeOH in DCM to afford the title compound (103 mg, 79%).

Workup

  1. extractionextracted with 2-MeTHF (50 mL)
  2. washThe organic layer was washed with brine (50 mL)
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography
  6. washeluting with 20-25% EtOAc in DCM
  7. dissolutionthe residue was dissolved in DCM (5 mL)
  8. stirringthe reaction was stirred at this temperature for 40 minutes
  9. customThe reaction was quenched by the addition of MeOH (1 mL)
  10. stirringstirred for 20 minutes
  11. concentrationThe reaction was concentrated in vacuo
  12. custompurified
  13. washeluting with 2-6% MeOH in DCM

Sources & evidence

ORD record
ord-313171deb3eb4e0bba9d0487bdf352fc
Source dataset
uspto-grants-2016_05
Patent number
US09328096B2

Reaction notes

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