Cesium fluoride → HCID 178462223, compound

HRID 1406318Notes

Reaction equation

HRID 1406318 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[CH:11][C:12]([OH:15])=[N:13][CH:14]=2)O1.Br[C:18]1[CH:19]=[C:20]([O:25][C@@H:26]([C:28]2[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=2[N:35]2[N:39]=[CH:38][CH:37]=[N:36]2)[CH3:27])[C:21]([NH2:24])=[N:22][CH:23]=1.[F-].[Cs+].B([O-])[O-]>CO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:24][C:21]1[N:22]=[CH:23][C:18]([C:9]2[CH:14]=[N:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[CH:19][C:20]=1[O:25][C@@H:26]([C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[N:35]1[N:39]=[CH:38][CH:37]=[N:36]1)[CH3:27]

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 67468125(R)-5-bromo-3-(1-(5-fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl)ethoxy)pyridin-2-amineHCID 178431084HCID 178431084, compoundHCID 178514824HCID 178514824, compound

Product 1

HCID 178462223HCID 178462223, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of the 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-ol (470 mg, 2.13 mmol), (R)-5-bromo-3-(1-(5-fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl)ethoxy)pyridin-2-amine of preparation 45 (510 mg, 1.35 mmol) and CsF (724 mg, 4.72 mmol) were taken up in MeOH (13 mL). The mixture was thoroughly degassed before Pd(dppf)Cl2 (55 mg, 0.067 mmol) was added and the mixture was heated in the microwave at 120° C. for 2 hr. LCMS showed the presence of starting materials. Additional portions of Pd(dppf)Cl2 (27 mg) and boronate (100 mg) were added. The mixture was degassed again and heated in the microwave at 120° C. for another 1 hr. LCMS indicated the complete consumption of bromide starting material. The mixture was filtered and the filtrate was concentrated. The residue was taken up in MeOH and purified by a reverse phase prep-HPLC to give the title compound (115 mg) as a fluffy white solid after lyophilization.

Workup

  1. additionwas added
  2. customThe mixture was degassed again
  3. temperatureheated in the microwave at 120° C. for another 1 hr
  4. customthe complete consumption of bromide starting material
  5. filtrationThe mixture was filtered
  6. concentrationthe filtrate was concentrated
  7. custompurified by a reverse phase prep-HPLC

Sources & evidence

ORD record
ord-25bc409831fa4bc291bc73bcdc659c5f
Source dataset
uspto-grants-2014_12
Patent number
US08916593B2

Reaction notes

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