Dichloromethane → ethyl ((1S)-5-{3-[[5-cyano-3-fluoro-6-(4-methoxyphenyl)-2-pyridinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

HRID 603475Notes

Reaction equation

HRID 603475 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]([CH3:28])[CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[C@H:18]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:17][CH2:16]3)[C:5]([F:29])=[CH:4][C:3]=1[C:30]#[N:31].C(=O)([O-])[O-].[Na+].[Na+].[CH3:38][O:39][C:40]1[CH:45]=[CH:44][C:43](B(O)O)=[CH:42][CH:41]=1.C(Cl)Cl>C1(C)C=CC=CC=1.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.O1CCOCC1>[C:30]([C:3]1[CH:4]=[C:5]([F:29])[C:6]([N:8]([CH3:28])[CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[C@H:18]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:17][CH2:16]3)=[N:7][C:2]=1[C:43]1[CH:44]=[CH:45][C:40]([O:39][CH3:38])=[CH:41][CH:42]=1)#[N:31]

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 86604602ethyl ((1S)-5-{3-[(6-chloro-5-cyano-3-fluoro-2-pyridinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

Product 1

HCID 68382765ethyl ((1S)-5-{3-[[5-cyano-3-fluoro-6-(4-methoxyphenyl)-2-pyridinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetateYield 88%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of ethyl ((1S)-5-{3-[(6-chloro-5-cyano-3-fluoro-2-pyridinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (Example 312, 0.10 g, 0.22 mmol) in a mixture of toluene (1.5 mL), 1,4-dioxane (0.5 mL), and water (0.6 mL) were added sodium carbonate (0.24 g, 2.24 mmol), 4-methoxyphenyl boronic acid (0.14 g, 0.90 mmol) and PdCl2(dppf).CH2Cl2 (0.04 g, 0.04 mmol). The mixture was heated at 80° C. for 4 h, and then concentrated under reduced pressure. The product (0.10 g, 88%) was isolated after silica gel flash chromatography (2:1 hexanes/EtOAc). 1H NMR (400 MHz, CD2Cl2) δ 7.87 (d, 2H), 7.37 (d, 1H), 7.04 (d, 1H), 6.98 (d, 2H), 6.72 (d, 1H), 6.65 (dd, 1H), 4.16 (q, 2H), 4.00 (t, 2H), 3.90-3.85 (m, 5H), 3.49 (qt, 1H), 3.30 (d, 3H), 2.94-2.76 (m, 2H), 2.70 (dd, 1H), 2.45-2.32 (m, 2H), 2.16 (qt, 2H), 1.80-1.70 (m, 1H), 1.29 (t, 3H).

Workup

  1. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f07e34fa55294ee7a67a0588f9d7afc8
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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