Potassium Carbonate → 2-[5-(4,5-Dihydro[1,2,4]triazolo[4,3-a]quinolin-7-yl)pyridin-3-yl]-1,1,1,3,3,3-hexafluoropropan-2-ol

HRID 1521591Notes

Reaction equation

HRID 1521591 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]([C:9]1[CH:10]=[C:11](B(O)O)[CH:12]=[N:13][CH:14]=1)([OH:8])[C:4]([F:7])([F:6])[F:5].Br[C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[N:27]1[CH:31]=[N:32][N:33]=[C:26]1[CH2:25][CH2:24]2.C(=O)([O-])[O-].[K+].[K+]>C(O)(C)(C)C.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH:31]1[N:27]2[C:28]3[C:23]([CH2:24][CH2:25][C:26]2=[N:33][N:32]=1)=[CH:22][C:21]([C:11]1[CH:10]=[C:9]([C:3]([OH:8])([C:4]([F:7])([F:6])[F:5])[C:2]([F:19])([F:18])[F:1])[CH:14]=[N:13][CH:12]=1)=[CH:30][CH:29]=3

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 21543699HCID 21543699, compoundHCID 89961718(5-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)pyridin-3-yl)boronic acid

Product 1

HCID 899615962-[5-(4,5-Dihydro[1,2,4]triazolo[4,3-a]quinolin-7-yl)pyridin-3-yl]-1,1,1,3,3,3-hexafluoropropan-2-ol

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
80 °C

Procedure

A vial containing the title compound from Example 61 Step B (15 mg, 0.05 mmol), the title compound from Example 22 Step B (11.7 mg, 0.047 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (3.68 mg, 5.19 μmol) and potassium carbonate (21.5 mg, 0.156 mmol) in tert-butanol (577 μL) and water (72 μL) was flushed with nitrogen, sealed tightly and heated to 80° C. overnight. The reaction solution was then cooled to room temperature and concentrated under reduced pressure. The resulting residue was diluted with acetonitrile and purified by HPLC (C18 column, 10 to 100% acetonitrile/water, both 0.1% v/v trifluoroacetic acid). Fractions containing product were combined, aqueous 1 M hydrochloric acid solution was added and the solution concentrated under reduced pressure to provide the title compound: LCMS m/z 414.79 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 9.38 (s, 1H), 9.11 (s, 1H), 8.85 (s, 1H), 8.27 (s, 1H), 7.92 (d, J=8.34 Hz, 1H) 7.87 (d, J=1.71 Hz, 1H), 7.81 (dd, J=1.94, 8.34 Hz, 1H), 3.15 (s, 4H).

Workup

  1. customsealed tightly
  2. temperatureThe reaction solution was then cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. additionThe resulting residue was diluted with acetonitrile
  5. custompurified by HPLC (C18 column, 10 to 100% acetonitrile/water
  6. additionFractions containing product
  7. additionaqueous 1 M hydrochloric acid solution was added
  8. concentrationthe solution concentrated under reduced pressure

Sources & evidence

ORD record
ord-1a4d51e581f944aa864ef31b0d3c155c
Source dataset
uspto-grants-2015_07
Patent number
US09073929B2

Reaction notes

Loading…