Cesium carbonate → HCID 86712706, compound

HRID 1779063Notes

Reaction equation

HRID 1779063 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]([O:21][CH3:22])=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:29]=[CH:28][C:27]([CH:30]2[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]2)=[CH:26][CH:25]=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]>[CH3:22][O:21][C:5]1[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])=[N:7][C:2]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([CH:30]3[CH2:31][CH2:32][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:34][CH2:35]3)=[CH:26][CH:25]=2)=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 21940085tert-Butyl 4-(4-aminophenyl)piperidine-1-carboxylateHCID 86712705HCID 86712705, compound

Product 1

HCID 86712706HCID 86712706, 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-methoxypyrimidin-4-yl)ethynyl)phenyl)acetate (A98) (0.10 g, 0.32 mmol) in 1,4-dioxane (6 mL) was added tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate (0.087 g, 0.32 mmol), Cs2CO3 (0.41 g, 1.3 mmol), Pd2(dba)3 (0.030 g, 0.032 mmol) and Xantphos (0.055 g, 0.095 mmol). The resulting mixture was degassed with nitrogen for 5 minutes, before heating under microwave irradiation for 30 minutes at 120° C., then for 60 minutes at 120° C. EtOAc (100 mL) was added and the mixture was washed with water (2×25 mL), brine (25 mL), dried (MgSO4) and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-25% EtOAc in petroleum benzine 40-60° C.) to give the title compound A99 as a yellow oil (0.11 g, 64%); 1H NMR (400 MHz, CDCl3) δ 8.18 (s, 1H), 7.66 (d, J=7.6 Hz, 1H), 7.52 (d, J=8.5 Hz, 2H), 7.43-7.29 (m, 3H), 7.16 (d, J=8.5 Hz, 2H), 6.98 (s, 1H), 4.38-4.17 (m, 2H), 4.02 (s, 2H), 3.94 (s, 3H), 3.70 (s, 3H), 2.80 (t, J=11.9 Hz, 2H), 2.62 (tt, J=12.0, 3.3 Hz, 1H), 1.82 (d, J=13.0 Hz, 2H), 1.68-1.51 (m, peak obscured), 1.49 (s, 9H). LCMS-A: rt 6.69 min; m/z 557.3 [M+H]+.

Workup

  1. customThe resulting mixture was degassed with nitrogen for 5 minutes
  2. additionEtOAc (100 mL) was added
  3. washthe mixture was washed with water (2×25 mL), brine (25 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-25% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-b449e6a446134135ac9bc27880dbd239
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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