Cesium carbonate → HCID 86712642, compound

HRID 1778973Notes

Reaction equation

HRID 1778973 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][C:17]([O:19][CH3:20])=[O:18])[C:5]([CH3:21])=[CH:4][N:3]=1.[NH2:22][C:23]1[CH:24]=[CH:25][C:26]([CH:29]2[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]2)=[N:27][CH:28]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:20][O:19][C:17](=[O:18])[CH2:16][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[C:9]#[C:8][C:6]1[C:5]([CH3:21])=[CH:4][N:3]=[C:2]([NH:22][C:23]2[CH:24]=[CH:25][C:26]([CH:29]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]3)=[N:27][CH:28]=2)[N:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59128562tert-Butyl 4-(5-aminopyridin-2-yl)piperidine-1-carboxylateHCID 86712625HCID 86712625, compound

Product 1

HCID 86712642HCID 86712642, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of methyl 2-(2-((2-chloro-5-methylpyrimidin-4-yl)ethynyl)phenyl)acetate (K7) (100 mg, 0.333 mmol) in 1,4-dioxane (8 mL) was added tert-butyl 4-(5-aminopyridin-2-yl)piperidine-1-carboxylate (K4) (92.2 mg, 0.333 mmol), Cs2CO3 (433 mg, 1.33 mmol), Pd2(dba)3 (30 mg, 0.033 mmol) and Xantphos (58 mg, 0.10 mmol). The resulting mixture was degassed with nitrogen for 5 minutes before heating under microwave irradiation for 30 minutes at 120° C. The resulting mixture was diluted with EtOAc (100 mL) then washed with water (2×25 mL), brine (25 mL), dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in hexanes) to give the title compound A17 as a yellow foam (112 mg, 62%); 1H NMR (400 MHz, CDCl3) δ 8.62 (d, J=2.4 Hz, 1H), 8.32 (d, J=0.6 Hz, 1H), 8.16 (dd, J=8.5, 2.7 Hz, 1H), 7.66 (dd, J=7.6, 0.9 Hz, 1H), 7.43-7.30 (m, 3H), 7.14 (d, J=8.5 Hz, 1H), 7.10 (s, 1H), 4.25 (br. s, 2H), 3.95 (s, 2H), 3.70 (s, 3H), 2.86-2.78 (m, 3H), 2.35 (d, J=0.4 Hz, 3H), 1.91 (d, J=13.3 Hz, 2H), 1.75-1.63 (m, 2H), 1.47 (s, 9H). LCMS-A: rt 5.462 min; m/z 542 [M+H]+.

Workup

  1. customThe resulting mixture was degassed with nitrogen for 5 minutes
  2. additionThe resulting mixture was diluted with EtOAc (100 mL)
  3. washthen washed with water (2×25 mL), brine (25 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b6747720719c450c9d415cb425a1cb0b
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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