Cesium carbonate → HCID 57561092, compound

HRID 1724835Notes

Reaction equation

HRID 1724835 reaction equation
Cl[C:2]1[C:11]2[C:6](=[N:7][C:8]([C:12]3[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:15]=[CH:14][N:13]=3)=[CH:9][CH:10]=2)[N:5]=[C:4]([CH2:22][O:23][CH3:24])[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][N:33]=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.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]>[CH3:24][O:23][CH2:22][C:4]1[CH:3]=[C:2]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]([F:40])([F:39])[F:41])=[CH:34][N:33]=2)[C:11]2[C:6](=[N:7][C:8]([C:12]3[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:15]=[CH:14][N:13]=3)=[CH:9][CH:10]=2)[N:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 7358622-Amino-5-(trifluoromethyl)pyridineHCID 57561127HCID 57561127, compound

Product 1

HCID 57561092HCID 57561092, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

To a de-gassed mixture of 4-chloro-2-methoxymethyl-7-(3-trifluoromethyl-pyridin-2-yl)-[1,8]naphthyridine (1 mmol), cesium carbonate (2 mmol), 2-amino-5-trifluoromethyl pyridine (1 mmol) in dioxane (10 mL) under nitrogen, add Pd2dba3 (0.05 mmol) and xantphos (0.05 mol). Stir the mixture at 90° C. overnight, concentrate, and extract with EtOAc. Dry over Na2SO4 and concentrate under vacuum. Purify by column chromatography eluting with dichloromethane/methanol/ammonium hydroxide mixture to give 2-methoxymethyl-7-[3-(trifluoromethyl) pyridin-2-yl]-N-[5-(trifluoromethyl)pyridin-2-yl]-[1,8]naphthyridin-4-amine. MS 480 (M+1). 1H NMR δ (CDCl3) 8.88 (1H, d), 8.62 (1H, s), 8.18 (1H, d), 8.07 (1H, s), 7.88 (1H, dd), 7.84 (1H, d), 7.56 (1H, d), 7.54 (1H, d), 7.30 (1H, d), 4.77 (2H, s), 3.52 (3H, s), 2.63 (1H, br s).

Workup

  1. concentrationconcentrate
  2. extractionextract with EtOAc
  3. dry with materialDry over Na2SO4
  4. concentrationconcentrate under vacuum
  5. customPurify by column chromatography
  6. washeluting with dichloromethane/methanol/ammonium hydroxide mixture

Sources & evidence

ORD record
ord-fe336eb581414cd7afe27a6f485597a4
Source dataset
uspto-grants-2009_02
Patent number
US07488740B2

Reaction notes

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