Cesium carbonate → HCID 90067689, compound

HRID 1057058Notes

Reaction equation

HRID 1057058 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH:8]2[CH2:11][N:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]2)[CH:5]=[C:4]([N:19]2[CH2:23][CH2:22][C:21]([F:25])([F:24])[CH2:20]2)[N:3]=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.[NH2:68][C:69]1[CH:74]=[C:73]([C:75]([F:78])([F:77])[F:76])[CH:72]=[CH:71][N:70]=1.O1CCOCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>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]>[F:25][C:21]1([F:24])[CH2:22][CH2:23][N:19]([C:4]2[CH:5]=[C:6]([CH:8]3[CH2:11][N:10]([C:12]([O:14][C:15]([CH3:17])([CH3:16])[CH3:18])=[O:13])[CH2:9]3)[CH:7]=[C:2]([NH:68][C:69]3[CH:74]=[C:73]([C:75]([F:77])([F:76])[F:78])[CH:72]=[CH:71][N:70]=3)[N:3]=2)[CH2:20]1

Participants

7

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 90015288HCID 90015288, compound

Product 1

HCID 90067689HCID 90067689, compoundYield 117.9%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

To a solution of tert-butyl 3-[2-chloro-6-(3,3-difluoropyrrolidin-1-yl)-4-pyridyl]azetidine-1-carboxylate (1-b, 582 mg, 1.557 mmol), Pd2(dba)3 (147 mg, 0.10 equiv., 0.1557 mmol), XantPhos (186 mg, 0.20 equiv., 0.3114 mmol), 2-amino-4-(trifluoromethyl)pyridine (765 mg, 3.0 equiv., 4.671 mmol) in 1,4-dioxane (5.3 mL, 62.28 mmol) was added cesium carbonate (2.03 g, 4.0 equiv., 6.228 mmol), and the reaction was kept at 150° C. for 60 min. The crude was purified by silica gel chromatography (0-60% EtOAc/Heptane) to yield 917 mg yellow powder (contaminated by 2-amino-4-(trifluoromethyl)pyridine). 1H NMR (400 MHz, CDCl3) δ (delta) 8.57 (s, 1H), 8.36 (d, J=5.1 Hz, 1H), 7.04 (d, J=5.2 Hz, 1H), 6.29 (s, 1H), 5.87 (s, 1H), 4.30 (t, J=8.6 Hz, 2H), 4.02-3.93 (m, 2H), 3.87 (t, J=13.1 Hz, 2H), 3.74 (t, J=7.2 Hz, 2H), 3.67-3.54 (m, 1H), 2.60-2.43 (m, 2H), 1.47 (s, 9H). LCMS: m/z 500 (M+H).

Workup

  1. customThe crude was purified by silica gel chromatography (0-60% EtOAc/Heptane)

Sources & evidence

ORD record
ord-6e2ec1daad5844c79eb131995f6be05c
Source dataset
uspto-grants-2016_07
Patent number
US09399636B2

Reaction notes

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