Cesium carbonate → [2-(5-Chloro-2-fluoro-phenyl)-quinolin-4-yl]-(3-methoxy-pyridin-4-yl)-amine

HRID 877282Notes

Reaction equation

HRID 877282 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=2[F:19])[CH:3]=1.[CH3:20][O:21][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][C:27]=1[NH2:28].C([O-])([O-])=O.[Cs+].[Cs+]>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].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>[Cl:18][C:16]1[CH:15]=[CH:14][C:13]([F:19])=[C:12]([C:4]2[CH:3]=[C:2]([NH:28][C:27]3[CH:26]=[CH:25][N:24]=[CH:23][C:22]=3[O:21][CH3:20])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH:17]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 30167383-Methoxy-4-aminopyridineHCID 671727124-Bromo-2-(5-chloro-2-fluoro-phenyl)-quinoline

Product 1

HCID 67175376[2-(5-Chloro-2-fluoro-phenyl)-quinolin-4-yl]-(3-methoxy-pyridin-4-yl)-amineYield 80.8%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

250 mg 4-Bromo-2-(5-chloro-2-fluoro-phenyl)-quinoline (cf. Example 5; M 336.59) and 94 mg of 3-methoxy-4-amino pyridine (Tyger Scientific) in 25 ml dioxane were treated under argon with 14 mg Pd2(dba)3 (Aldrich) and 22 mg Xanthphos (ABCR) under basic conditions adjusted with 485 mg Cs2CO3 at 85° C. internal temperature over night. Work-up was conducted by RP HPLC on a Gemini column Axia RP18-100×30 mm/10 μm-110 A. Elution was performed with a 30 min gradient of 1-99% buffer B (=0.3% TFA in CH3CN) in buffer A (=0.3% TFA in water) at 30 ml/min and monitoring at 215 nm. Pooled material after drying yielded 228 mg product of correct mass M+H+ 380 and Rt˜1.74 min in LC-MS system 2.

Workup

  1. washElution
  2. customPooled material after drying

Sources & evidence

ORD record
ord-6683359edc2b4153b8adbf0aa95a789e
Source dataset
uspto-grants-2015_03
Patent number
US08987301B2

Reaction notes

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