Triethylamine → HCID 73336015, compound

HRID 710669Notes

Reaction equation

HRID 710669 reaction equation
[Cl:1][C:2]1[C:3]([C:12]([F:15])([F:14])[F:13])=[N:4][N:5]([CH2:8][C:9]([OH:11])=O)[C:6]=1[CH3:7].CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:47][C:48]1[CH:53]=[CH:52][C:51]([N:54]2[C:62]3[CH2:61][CH2:60][CH:59]([C:63]([O:65][CH3:66])=[O:64])[NH:58][C:57]=3[CH:56]=[N:55]2)=[CH:50][CH:49]=1>CN(C=O)C.O>[Cl:1][C:2]1[C:3]([C:12]([F:15])([F:14])[F:13])=[N:4][N:5]([CH2:8][C:9]([N:58]2[CH:59]([C:63]([O:65][CH3:66])=[O:64])[CH2:60][CH2:61][C:62]3[N:54]([C:51]4[CH:50]=[CH:49][C:48]([F:47])=[CH:53][CH:52]=4)[N:55]=[CH:56][C:57]2=3)=[O:11])[C:6]=1[CH3:7]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 1876853(4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86711684HCID 86711684, compound

Product 1

HCID 73336015HCID 73336015, compoundYield 11%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-[4-chloro-5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetic acid (20 mg, 0.073 mmol) in DMF (2 mL) was added Et3N (50 μL, 0.219 mmol), HATU (55 mg, 0.145 mmol) followed by methyl 1-(4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[4,3-b]pyridine-5-carboxylate (20 mg, 0.073 mmol) at room temperature. The resulting solution was then stirred at 80° C. for 5 h. The reaction mixture was then cooled to room temperature, H2O (10 mL) was added and the mixture was extracted with EtOAc (2×15 mL). The combined EtOAc layers were dried (MgSO4), filtered, concentrated in vacuo and the resulting crude product was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give the desired product as white powder (0.004 g, 0.008 mmol, 7%). 1H NMR (400 MHz, CD3OD) δ 8.28 (s, 1H), 7.52 (2H, dd, J=5, 9 Hz), 7.26 (2H, t, 8.6, J=17.2 Hz), 5.3 (2H, dd, J=17.2, 69.2 Hz), 3.83 (s, 3H), 2.80-2.82 (m, 2H), 2.29 (s, 3H), 2.15-2.17 (m, 2H); MS: (ES) m/z calculated for C21H18ClF4N5O3 [M+H]+ 500.1, found 500.1.

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. extractionthe mixture was extracted with EtOAc (2×15 mL)
  3. dry with materialThe combined EtOAc layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customthe resulting crude product was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-1e625849ebcb455abcbeda99cdaf7401
Source dataset
uspto-grants-2015_11
Patent number
US09181241B2

Reaction notes

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