Potassium Phosphate, Tribasic → HCID 53255362, compound

HRID 1497318Notes

Reaction equation

HRID 1497318 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=[C:11]([C:19]([NH:21][C@H:22]3[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]3[OH:28])=[O:20])[CH:10]=2)=[CH:4][CH:3]=1.[CH3:29][N:30]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[N:31]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[OH:28][C@H:23]1[CH2:24][CH2:25][CH2:26][CH2:27][C@@H:22]1[NH:21][C:19]([C:11]1[CH:10]=[C:9]([CH2:8][C:5]2[CH:6]=[N:7][C:2]([C:33]3[CH:32]=[N:31][N:30]([CH3:29])[CH:34]=3)=[CH:3][CH:4]=2)[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=1)=[O:20]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 53307538HCID 53307538, compound

Product 1

HCID 53255362HCID 53255362, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

To a microwave vial containing 4-[(6-chloropyridin-3-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide (A) (100 mg, 0.25 morel), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-pyrazole (63 mg, 0.30 mmol), Pd2(dba)3 (2.3 mg, 2.5 μmol), and tricyclohexylphosphine (1.7 mg, 6.1 mop was added 0.84 mL of dioxane and 0.34 mL 1.7 M aqueous tribasic potassium phosphate. The reaction was heated to 140° C. in a microwave reactor for 1 h. The reaction mixture was extracted with ethyl acetate, dried over sodium sulfate, filtered, and concentrated. The resultant residue was subjected to purification via reverse phase HPLC to afford the title compound that gave a mass ion (ES+) of 442.2241 for M+H+. 1H NMR (400 MHz, CDCl3) δ 8.49 (d, J=2.0 Hz, 1H), 8.27 (d, J=7.3 Hz, 1H), 8.19 (s, 1H), 8.14 (d, J=8.6, 1H), 8.04 (d, J=8.4 Hz, 1H), 7.88 (d, J=9.7 Hz, 2H), 7.75 (t, J=7.1 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.39 (dd, J=2.0, 8.1 Hz, 1H), 7.33 (d, J=8.2 Hz, 2H), 4.48 (s, 2H), 3.94 (s, 3H), 3.91-3.84 (m, 1H), 3.58 (m, 1H), 3.38 (br s, 1H) 2.16-2.13 (m, 2H), 1.92-1.79 (m, 2H), 1.52-1.31 (m, 4H).

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resultant residue was subjected to purification via reverse phase HPLC

Sources & evidence

ORD record
ord-acd2bfd829c84f0eb2373c134b2446b1
Source dataset
uspto-grants-2015_12
Patent number
US09199939B2

Reaction notes

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