Potassium Phosphate, Tribasic → 4-(6-(3,6-dihydro-2H-pyran-4-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-pyridinyl)quinoline

HRID 1618667Notes

Reaction equation

HRID 1618667 reaction equation
Br[C:2]1[CH:3]=[C:4]2[N:10]([C:11]3[C:20]4[C:15](=[CH:16][C:17]([F:21])=[CH:18][CH:19]=4)[N:14]=[C:13]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[C:12]=3[CH3:28])[CH2:9][C:8]([CH3:30])([CH3:29])[C:5]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+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[O:31]1[CH2:32][CH:33]=[C:34]([C:2]2[CH:3]=[C:4]3[N:10]([C:11]4[C:20]5[C:15](=[CH:16][C:17]([F:21])=[CH:18][CH:19]=5)[N:14]=[C:13]([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=5)[C:12]=4[CH3:28])[CH2:9][C:8]([CH3:30])([CH3:29])[C:5]3=[N:6][CH:7]=2)[CH2:35][CH2:36]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 672855904-(6-Bromo-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline

Product 1

HCID 509397294-(6-(3,6-dihydro-2H-pyran-4-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-pyridinyl)quinoline

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-(6-bromo-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (150 mg, 0.324 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (102 mg, 0.486 mmol), potassium phosphate tribasic (206 mg, 0.971 mmol), Pd(OAc)2 (72.7 mg, 0.324 mmol) and SPhos (26.6 mg, 0.065 mmol) in toluene (2.5 mL) was heated in the microwave for 1 h at 100° C. After this time the reaction was partitioned between EtOAc (60 mL) and water (30 mL). The separated organic layer was dried over MgSO4, filtered and evaporated in vacuo. Column chromatography (hexanes:EtOAc, 1:0 to 0:1 as eluent) gave 4-(6-(3,6-dihydro-2H-pyran-4-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-pyridinyl)quinoline. 1H NMR (500 MHz, chloroform-d) δ ppm 8.71-8.77 (1H, m), 7.97 (1H, d, J=2.0 Hz), 7.83-7.94 (3H, m), 7.79 (1H, dd, J=9.3, 5.9 Hz), 7.41 (1H, ddd, J=7.3, 4.9, 1.5 Hz), 7.30 (1H, ddd, J=9.2, 8.1, 2.6 Hz), 6.20 (1H, d, J=1.7 Hz), 5.90-5.95 (1H, m), 4.18-4.27 (2H, m), 3.78-3.90 (4H, m), 2.29-2.44 (5H, m), 1.61 (3H, s), 1.55 (3H, s). Mass Spectrum (ESI) m/e=467.2 (M+1).

Workup

  1. customAfter this time the reaction was partitioned between EtOAc (60 mL) and water (30 mL)
  2. dry with materialThe separated organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated in vacuo

Sources & evidence

ORD record
ord-a5a0eb5b389f464fbb93f6ef1357ccb5
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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