Diisopropylethylamine → HCID 90410567, compound

HRID 2177595Notes

Reaction equation

HRID 2177595 reaction equation
[NH:1]1[C:5]2[CH2:6][NH:7][CH2:8][CH2:9][C:4]=2[CH:3]=[N:2]1.[Cl:10][C:11]1[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:17]=[CH:16][C:12]=1[C:13](O)=[O:14].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>CN(C=O)C>[Cl:10][C:11]1[C:19]([C:20]([F:22])([F:23])[F:21])=[CH:18][CH:17]=[CH:16][C:12]=1[C:13]([N:7]1[CH2:8][CH2:9][C:4]2[CH:3]=[N:2][NH:1][C:5]=2[CH2:6]1)=[O:14]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27366772-Chloro-3-(trifluoromethyl)benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 219528564,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine(SALTDATA: 2HCl)

Product 1

HCID 90410567HCID 90410567, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (1.01 g, 5.15 mmol) in DMF (17 mL) was added 2-chloro-3-(trifluoromethyl)benzoic acid (2.31 g, 10.30 mmol), Hunig's base (3.55 mL, 20.60 mmol) and HATU (2.31 g, 10.30 mmol). The solution was allowed to stir for 30 min at rt then poured into ice water (300 mL). The resulting solid was collected by suction filtration and allowed to air dry. The solid was purified by chromatography on silica gel (0-100% ethyl acetatehexanes). The product fractions were concentrated to a white solid which was dissolved in ethanol (20 mL) and 1M NaOH (20 mL) and stirred at 80° C. for 1 h. Water (50 mL) and CH2Cl2 (50 mL) were added. The layers were separated and the water layer was extracted two times with CH2Cl2. The organic layers were combined, dried over anhydrous MgSO4, filtered and concentrated to an oil (1.37 g, 81%). MS (ESI) mass calcd. C14H11ClF3N3O, 329.1. m/z found, 330.1 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 7.79-7.73 (m, 1H), 7.52-7.41 (m, 2H), 7.37 (br s, 1H), 5.11 (d, J=16.6 Hz, 0.5H), 4.85 (d, J=16.6 Hz, 0.5H), 4.46 (d, J=15.9 Hz, 0.5H), 4.36 (d, J=15.9 Hz, 0.5H), 4.22-4.18 (m, 0.5H), 3.94-3.88 (m, 0.5H), 3.49-3.44 (m, 1H), 2.85-2.80 (m, 1H), 2.75-2.65 (m, 1H), 2.62-2.54 (m, 1H).

Workup

  1. filtrationThe resulting solid was collected by suction filtration
  2. customto air dry
  3. customThe solid was purified by chromatography on silica gel (0-100% ethyl acetatehexanes)
  4. concentrationThe product fractions were concentrated to a white solid which
  5. dissolutionwas dissolved in ethanol (20 mL)
  6. stirring1M NaOH (20 mL) and stirred at 80° C. for 1 h
  7. additionWater (50 mL) and CH2Cl2 (50 mL) were added
  8. customThe layers were separated
  9. extractionthe water layer was extracted two times with CH2Cl2
  10. dry with materialdried over anhydrous MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated to an oil (1.37 g, 81%)

Sources & evidence

ORD record
ord-2e39b4fd2a2d4e929a09f6a5bfec6b80
Source dataset
uspto-grants-2015_06
Patent number
US09066946B2

Reaction notes

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