Stannanecarbonitrile, tributyl- → HCID 59631525, compound

HRID 1431761Notes

Reaction equation

HRID 1431761 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:14]([C:16]2[C:25]3[C:20](=[CH:21][C:22]([F:26])=[CH:23][CH:24]=3)[N:19]=[C:18]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=3)[C:17]=2[CH3:33])[OH:15])[CH:5]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:7]=1.C([Sn]([C:47]#[N:48])(CCCC)CCCC)CCC>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].CN1C(=O)CCC1>[F:26][C:22]1[CH:21]=[C:20]2[C:25]([C:16]([CH:14]([OH:15])[C:4]3[CH:3]=[C:2]([CH:7]=[C:6]([N:8]4[CH2:13][CH2:12][O:11][CH2:10][CH2:9]4)[CH:5]=3)[C:47]#[N:48])=[C:17]([CH3:33])[C:18]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=3)=[N:19]2)=[CH:24][CH:23]=1

Participants

5

Reactant 2

HCID 200512Stannanecarbonitrile, tributyl-HCID 59631266HCID 59631266, compound

Product 1

HCID 59631525HCID 59631525, compound

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of (3-chloro-5-morpholinophenyl)(7-fluoro-3-methyl-2-(pyridin-2-yl)-quinolin-4-yl)methanol (0.050 g, 0.108 mmol), tributyltin cyanide (0.034 g, 0.108 mmol), XPhos precatalyst (CAS 1028206-56-5; 0.014 g, 0.022 mmol), and NMP (1.0 mL) was heated in a microwave at 150° C. for 2 h. Upon completion, the reaction mixture was partitioned between EtOAc and water, and the organic phase was dried over magnesium sulfate and concd. This afforded a crude material that was purified by column chromatography (silica; 0-100% EtOAc in hexanes) to yield 3-((7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)(hydroxy)methyl)-5-morpholinobenzonitrile as an amorphous beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.70 (1H, d), 8.31 (1H, m), 8.01 (1H, d, J=1.8 Hz), 7.83 (1H, d, J=7.8 Hz), 7.72 (1H, d), 7.51 (1H, m), 7.41 (1H, m), 7.33 (1H, s), 7.24 (1H, s), 6.85 (1H, s), 6.75 (1H, d, J=4.3 Hz), 6.59 (1H, d), 3.71 (4H, t, J=4.8 Hz), 3.14 (4H, q, J=4.4 Hz), 2.46 (3H, s). Mass Spectrum (ESI) m/e=455.0 (M+1).

Workup

  1. customUpon completion, the reaction mixture was partitioned between EtOAc and water
  2. dry with materialthe organic phase was dried over magnesium sulfate and concd
  3. customThis afforded a crude material that
  4. customwas purified by column chromatography (silica; 0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-153578cb9ba749ff9dea61ac57731d67
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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