Potassium Phosphate, Tribasic → HCID 58547844, compound

HRID 2207846Notes

Reaction equation

HRID 2207846 reaction equation
Br[C:2]1[C:3]([O:16][CH:17]2[CH2:20][N:19]([C:21]3[CH:30]=[CH:29][C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]=3)[CH2:18]2)=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([CH2:14][OH:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[O:31]1[CH2:36][CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH2:33][CH2:32]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[O:31]1[CH2:32][CH:33]=[C:34]([C:2]2[C:3]([O:16][CH:17]3[CH2:20][N:19]([C:21]4[CH:30]=[CH:29][C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[N:22]=4)[CH2:18]3)=[N:4][C:5]([N:8]3[CH2:13][CH2:12][CH:11]([CH2:14][OH:15])[CH2:10][CH2:9]3)=[N:6][CH:7]=2)[CH2:35][CH2:36]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 58547731HCID 58547731, compound

Product 1

HCID 58547844HCID 58547844, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of (1-(5-bromo-4-((1-(quinolin-2-yl)azetidin-3-yl)oxy)pyrimidin-2-yl)piperidin-4-yl)methanol (see PREPARATION P7.1; 115 mg, 0.25 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (52.5 mg, 0.25 mmol) and K3PO4 (100 mg, 0.5 mmol) in 1,4-dioxane (10 mL) and H2O (2 mL) was added Pd(dppf)Cl2 (15 mg, 0.02 mmol) then the reaction mixture was stirred at 110° C. under N2 atmosphere overnight. The reaction mixture was filtered through CELITE® and washed with CH2Cl2 (30 mL). The filtrate was concentrated and the crude product was purified by silica gel column to give (1-(5-(3,6-dihydro-2H-pyran-4-yl)-4-((1-(quinolin-2-yl)azetidin-3-yl)oxy)pyrimidin-2-yl)piperidin-4-yl)methanol (100 mg, 0.21 mmol, yield 84%). ESI-MS (M+1): 474 calc. for C27H31N5O3 473.

Workup

  1. filtrationThe reaction mixture was filtered through CELITE®
  2. washwashed with CH2Cl2 (30 mL)
  3. concentrationThe filtrate was concentrated
  4. customthe crude product was purified by silica gel column

Sources & evidence

ORD record
ord-daf3652640bd4b148c4a616c12430f98
Source dataset
uspto-grants-2016_06
Patent number
US09376450B2

Reaction notes

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