Cesium carbonate → HCID 86712729, compound

HRID 1779096Notes

Reaction equation

HRID 1779096 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]=[N:25][N:26]([CH:28]2[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]2)[CH:27]=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]=[N:25][N:26]([CH:28]3[CH2:29][CH2:30][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:32][CH2:33]3)[CH:27]=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 27281520tert-butyl 4-(4-amino-1H-pyrazol-1-yl)piperidine-1-carboxylateHCID 86712625HCID 86712625, compound

Product 1

HCID 86712729HCID 86712729, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A suspension of methyl 2-(2-((2-chloro-5-methylpyrimidin-4-yl)ethynyl)phenyl)acetate (K7) (0.100 g, 0.333 mmol), tert-butyl 4-(4-amino-1H-pyrazol-1-yl)piperidine-1-carboxylate (A124) (0.089 g, 0.333 mmol), Cs2CO3 (0.433 g, 1.33 mmol), Pd2(dba)3 (0.030 g, 0.033 mmol) and Xantphos (0.058 g, 0.100 mmol) in 1,4-dioxane (6 mL) 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) and washed with water (2×25 mL), brine (25 mL), dried (Na2SO4) then concentrated under reduced pressure. The resulting brown oil was purified by silica gel column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-100% EtOAc in hexanes) to give the title compound A125 as a yellow foam (0.096 g, 54%); 1H NMR (400 MHz, CDCl3) δ 8.21 (s, 1H), 7.89 (s, 1H), 7.57 (dd, J=7.6, 1.3 Hz, 1H), 7.44 (s, 1H), 7.36-7.22 (m, 2H), 7.19 (s, 1H), 6.87 (s, 1H), 4.22-4.12 (m, 3H), 3.88 (s, 2H), 3.62 (s, 3H), 2.82 (t, J=11.9 Hz, 2H), 2.26 (s, 3H), 2.11-2.02 (m, 2H), 1.89 (qd, J=12.4, 4.4 Hz, 2H), 1.40 (s, 9H). LCMS-A: rt 6.358 min; m/z 531 [M+H]+.

Workup

  1. customwas degassed with nitrogen for 5 minutes
  2. additionThe resulting mixture was diluted with EtOAc (100 mL)
  3. washwashed with water (2×25 mL), brine (25 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationthen concentrated under reduced pressure
  6. customThe resulting brown oil was purified by silica gel column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-798eee9f7038410d9e80195dba370ce4
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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