Diisopropylethylamine → HCID 73335227, compound

HRID 710641Notes

Reaction equation

HRID 710641 reaction equation
[CH3:1][C:2]1[N:6]([CH:7]([CH2:11][CH3:12])[C:8]([OH:10])=O)[N:5]=[C:4]([C:13]([F:16])([F:15])[F:14])[CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[F:50][C:51]1[CH:56]=[CH:55][C:54]([N:57]2[C:65]3[CH2:64][CH2:63][CH2:62][NH:61][C:60]=3[CH:59]=[N:58]2)=[CH:53][CH:52]=1>O.C(OCC)(=O)C.CN(C)C=O>[F:50][C:51]1[CH:52]=[CH:53][C:54]([N:57]2[C:65]3[CH2:64][CH2:63][CH2:62][N:61]([C:8](=[O:10])[CH:7]([N:6]4[C:2]([CH3:1])=[CH:3][C:4]([C:13]([F:16])([F:15])[F:14])=[N:5]4)[CH2:11][CH3:12])[C:60]=3[CH:59]=[N:58]2)=[CH:55][CH:56]=1

Participants

8

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)HCID 19576698α-Ethyl-5-methyl-3-(trifluoromethyl)-1H-pyrazole-1-acetic acidHCID 679846101-(4-fluorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridine

Product 1

HCID 73335227HCID 73335227, compoundYield 92%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Dimethylformamide (0.7 mL) was added to a mixture containing 2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]butyric acid (50.5 mg, 0.214 mmol) and HATU (84.1 mg, 0.221 mmol). Diisopropylethylamine (92 μL, 0.53 mmol) was added at room temperature and the reaction mixture was stirred for 1 minute. 1-(4-Fluorophenyl)-4,5,6,7-tetrahydropyrazolo[4,3-b]pyridine (44.1 mg, 0.203 mmol) was then added all at once and the reaction mixture was stirred at room temperature overnight. Ethyl acetate and water were added and the layers were separated. The aqueous layer was extracted twice more with ethyl acetate. The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (SiO2, 17-33% ethyl acetate in hexanes) to afford the desired product as a white solid (80.9 mg, 0.186 mmol, 92%). 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.44 (ddd, J=8.8, 5.2, 2.0 Hz, 2H), 7.15 (ddd, J=8.4, 8.4, 2.0 Hz, 2H), 6.30 (s, 1H), 5.32 (dd, J=8.4, 6.8 Hz, 1H), 3.78 (ddd, J=12, 7.2, 2.8 Hz, 1H), 3.47 (ddd, J=12, 8.8, 3.2 Hz, 1H), 2.69-2.81 (m, 2H), 2.31 (s, 3H), 2.18-2.38 (m, 2H), 1.88-1.97 (m, 1H), 1.74-1.83 (m, 1H), 0.98 (t, J=7.2 Hz, 3H); MS: (ES) m/z calculated for C21H21N5OF4 [M+H]+ 436, found 436.

Workup

  1. stirringwas stirred at room temperature overnight
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted twice more with ethyl acetate
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified by flash chromatography (SiO2, 17-33% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-6a7c1d6cf5b04401947f44db5e1e6415
Source dataset
uspto-grants-2015_11
Patent number
US09181241B2

Reaction notes

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