Cesium carbonate → HCID 90067636, compound

HRID 1057064Notes

Reaction equation

HRID 1057064 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:5]=[C:4]([N:14]2[CH2:18][CH2:17][C:16]([F:20])([F:19])[CH2:15]2)[N:3]=1.[NH2:21][C:22]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][N:23]=1.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.C(=O)([O-])[O-].[Cs+].[Cs+]>O.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].CCOC(C)=O>[F:19][C:16]1([F:20])[CH2:17][CH2:18][N:14]([C:4]2[N:3]=[C:2]([NH:21][C:22]3[CH:27]=[C:26]([C:28]([F:30])([F:29])[F:31])[CH:25]=[CH:24][N:23]=3)[CH:7]=[C:6]([C:8]3[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=3)[CH:5]=2)[CH2:15]1

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27783152-Amino-4-(trifluoromethyl)pyridineHCID 90015001HCID 90015001, compound

Product 1

HCID 90067636HCID 90067636, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
180 °C

Procedure

To a mixture of 2-chloro-6-(3,3-difluoropyrrolidin-1-yl)-4-(3-pyridyl)pyridine (2-b, 63 mg, 0.2131 mmol), 2-amino-4-(trifluoromethyl)PYRIDINE (70 mg, 2.0 equiv., 0.4261 mmol), XantPhos (25 mg, 0.20 equiv., 0.04261 mmol), Pd2(dba)3 (20 mg, 0.10 equiv., 0.02131 mmol) in 1,4-dioxane (2.4 mL, 130 equiv., 27.70 mmol) was added cesium carbonate (208 mg, 3.0 equiv., 0.6392 mmol), and the reaction was maintained at 180° C. for 90 min. The crude was diluted with water, and extraction was done with EtOAc. After evaporation of the organic layers, the crude was purified via silica gel chromatography (0-100% EtOAc/Heptane) to 60 mg (67% after two steps) brown solid. 1H NMR (400 MHz, CDCl3) δ (delta) 8.86 (s, 1H), 8.66 (d, J=4.8 Hz, 1H), 8.58 (s, 1H), 8.38 (d, J=5.2 Hz, 1H), 7.89 (d, J=7.9 Hz, 1H), 7.46 (s, 1H), 7.43-7.35 (m, 1H), 7.05 (d, J=5.2 Hz, 1H), 6.55 (s, 1H), 6.10 (s, 1H), 3.93 (t, J=13.1 Hz, 2H), 3.79 (t, J=7.3 Hz, 2H), 2.62-2.47 (m, 2H). LCMS: m/z 422 (M+H).

Workup

  1. customAfter evaporation of the organic layers
  2. customthe crude was purified via silica gel chromatography (0-100% EtOAc/Heptane) to 60 mg (67% after two steps) brown solid

Sources & evidence

ORD record
ord-55a724a86ed140c499a0fc8193bc7cb1
Source dataset
uspto-grants-2016_07
Patent number
US09399636B2

Reaction notes

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