Diisopropylethylamine → HCID 178523077, compound

HRID 522080Notes

Reaction equation

HRID 522080 reaction equation
[Cl:1][C:2]1[CH:24]=[CH:23][C:22]([C:25]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][N:26]=2)=[CH:21][C:3]=1[C:4]([NH:6][C:7]1[N:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:10]=[C:9]([C:18]([OH:20])=O)[CH:8]=1)=[O:5].[NH:32]1[CH:36]=[C:35]([CH2:37][NH2:38])[N:34]=[N:33]1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl.CN(C)C=O>[NH:32]1[CH:36]=[C:35]([CH2:37][NH:38][C:18]([C:9]2[CH:8]=[C:7]([NH:6][C:4](=[O:5])[C:3]3[CH:21]=[C:22]([C:25]4[C:30]([F:31])=[CH:29][CH:28]=[CH:27][N:26]=4)[CH:23]=[CH:24][C:2]=3[Cl:1])[N:11]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:10]=2)=[O:20])[N:34]=[N:33]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 1184971095-(2-chloro-5-(3-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylic acidHCID 178510448HCID 178510448, compound

Product 1

HCID 178523077HCID 178523077, compoundYield 21.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(2-chloro-5-(3-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylic acid (Example 105, 200 mg, 0.458 mmol), (1H-1,2,3-triazol-4-yl)methanamine (74 mg, 0.549 mmol) and N,N-diisopropylethylamine (406 μL, 2.29 mmol) in dichloromethane (3 mL) and N,N-dimethylformamide (1 mL) was added HATU (261 mg, 0.687 mmol). The reaction was stirred at room temperature for 2 hours. Further HATU (87 mg, 0.229 mmol) was added and the reaction continued for 3 hours. The reaction solution was partitioned between water (10 mL) and ethyl acetate (10 mL). The aqueous layer was further extracted with ethyl acetate (2×10 mL), and the combined organic layers were washed with brine (20 mL), dried over magnesium sulphate and concentrated in vacuo. The residue was purified by elution through an SCX-2 column using MeOH followed by 7N NH3 in MeOH followed by silica gel column chromatography eluting with 1% NH3(aq) and 8% MeOH in DCM to afford the title compound as white solid (51 mg, 21%).

Workup

  1. waitthe reaction continued for 3 hours
  2. customThe reaction solution was partitioned between water (10 mL) and ethyl acetate (10 mL)
  3. extractionThe aqueous layer was further extracted with ethyl acetate (2×10 mL)
  4. washthe combined organic layers were washed with brine (20 mL)
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by elution through an SCX-2 column
  8. washeluting with 1% NH3(aq) and 8% MeOH in DCM

Sources & evidence

ORD record
ord-b67d8c3d4a59439ab11a1d6c40f2f7d4
Source dataset
uspto-grants-2016_05
Patent number
US09328096B2

Reaction notes

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