tert-Butanol → 7-{5-[1(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)cyclopropyl]-3-pyridinyl}-4,5-dihydro[1,2,4]triazolo[4,3-a]quinoline

HRID 1521611Notes

Reaction equation

HRID 1521611 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]1[CH:12]=[N:13][N:14]=[C:7]1[CH2:6][CH2:5]2.[CH:15]1([C:18]2[N:22]=[C:21]([C:23]3([C:26]4[CH:27]=[C:28](B(O)O)[CH:29]=[N:30][CH:31]=4)[CH2:25][CH2:24]3)[O:20][N:19]=2)[CH2:17][CH2:16]1.C(=O)([O-])[O-].[K+].[K+].C(O)(C)(C)C>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.O>[CH:15]1([C:18]2[N:22]=[C:21]([C:23]3([C:26]4[CH:27]=[C:28]([C:2]5[CH:3]=[C:4]6[C:9](=[CH:10][CH:11]=5)[N:8]5[CH:12]=[N:13][N:14]=[C:7]5[CH2:6][CH2:5]6)[CH:29]=[N:30][CH:31]=4)[CH2:25][CH2:24]3)[O:20][N:19]=2)[CH2:17][CH2:16]1

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 11430Potassium CarbonateHCID 21543699HCID 21543699, compoundHCID 89961641[5-[1-(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)cyclopropyl]-3-pyridinyl]boronic acid

Product 1

HCID 899615587-{5-[1(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)cyclopropyl]-3-pyridinyl}-4,5-dihydro[1,2,4]triazolo[4,3-a]quinoline

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

To a vial containing the title compound from Example 22 Step B (0.025 g, 0.100 mmol), the title compound from Example 72 Step C (0.027 g, 0.100 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (1.4 mg, 2.0 μmol), and potassium carbonate (0.041 g, 0.300 mmol) were added tert-butanol (1.1 mL) and water (0.14 mL). The vial 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 material 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 N HCl solution was added, and the resulting solution concentrated under reduced pressure to provide the title compound: LCMS m/z 397.02 [M+H]+; 1H NMR (500 MHz, CD3OD) δ 9.37 (s, 1H), 9.01 (s, 1H), 8.85 (s, 1H), 8.60 (s, 1H), 7.92-7.86 (m, 3H), 3.27-3.24 (m, 4H), 2.02-1.99 (m, 1H), 1.92-1.90 (m, 2H), 1.78-1.76 (m, 2H), 1.04-1.00 (m, 2H), 0.91-0.89 (m, 2H).

Workup

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

Sources & evidence

ORD record
ord-a0e80ca5049349ae897677587364ed1b
Source dataset
uspto-grants-2015_07
Patent number
US09073929B2

Reaction notes

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