Potassium Phosphate, Tribasic → HCID 56597376, compound

HRID 711271Notes

Reaction equation

HRID 711271 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][CH2:11][C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)=[N:16][CH:17]=2)=[O:9])=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:36]2[CH:37]=[CH:38][C:39]([N:42]3[CH2:46][CH2:45][CH2:44][C:43]3=[O:47])=[N:40][CH:41]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:47]=[C:43]1[CH2:44][CH2:45][CH2:46][N:42]1[C:39]1[N:40]=[CH:41][C:36]([C:2]2[CH:7]=[N:6][C:5]([C:8]([NH:10][CH2:11][C:12]3[CH:13]=[CH:14][C:15]([C:18]4[CH:23]=[CH:22][N:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=4)=[N:16][CH:17]=3)=[O:9])=[CH:4][CH:3]=2)=[CH:37][CH:38]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 457864871-[5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]-2-pyrrolidinoneHCID 68079864HCID 68079864, compound

Product 1

HCID 56597376HCID 56597376, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
96 °C

Procedure

A mixture of 5-bromo-N-((2′-(trifluoromethyl)-[2,4′-bipyridin]-5-yl)methyl)picolinamide 72-1 (22 mg, 0.05 mmol), 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)pyrrolidin-2-one 72-2 (29 mg, 0.1 mmol), Pd(PPh3)4 (12 mg, 0.01 mmol) and K3PO4 (21 mg, 0.1 mmol) in dioxane (0.5 mL) and water (0.1 mL) was stirred at 96° C. under argon overnight. After cooling to room temperature, the mixture was filtered through celite (washed with ethyl acetate) and the filtrate was redistributed between ethyl acetate and water. The organic phase was dried over Na2SO4 and concentrated with rotavap. The residue was subjected to preparative reverse phase HPLC separation to give 6′-(2-oxopyrrolidin-1-yl)-N-((2′-(trifluoromethyl)-[2,4′-bipyridin]-5-yl)methyl)-[3,3′-bipyridine]-6-carboxamide 72 as a solid. MS m/z 519.2 (M+1). 1H NMR 400 MHz (CDCl3) δ 8.83 (d, 1H), 8.79 (d, 1H), 8.76 (dd, 1H), 8.62 (dd, 1H), 8.57 (dd, 1H), 8.52 (t, 1H), 8.34-8.29 (m, 2H), 8.10-8.02 (m, 2H), 7.96-7.88 (m, 2H), 7.84 (d, 1H), 4.79 (d, 2H), 4.16 (t, 2H), 2.71 (t, 2H), 2.18 (t, 2H).

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered through celite (washed with ethyl acetate)
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationconcentrated with rotavap
  5. customThe residue was subjected to preparative reverse phase HPLC separation

Sources & evidence

ORD record
ord-e816c0cdb36841d5922a7343905eb5fe
Source dataset
uspto-grants-2015_11
Patent number
US09181235B2

Reaction notes

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