tert-Butanol → HCID 66576768, compound

HRID 1521606Notes

Reaction equation

HRID 1521606 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.[CH3:15][O:16][C:17]([C:19]1([C:22]2[CH:23]=[C:24](B(O)O)[CH:25]=[N:26][CH:27]=2)[CH2:21][CH2:20]1)=[O:18].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:12]1[N:8]2[C:9]3[C:4]([CH2:5][CH2:6][C:7]2=[N:14][N:13]=1)=[CH:3][C:2]([C:24]1[CH:23]=[C:22]([C:19]2([C:17]([O:16][CH3:15])=[O:18])[CH2:20][CH2:21]2)[CH:27]=[N:26][CH:25]=1)=[CH:11][CH:10]=3

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 11430Potassium CarbonateHCID 21543699HCID 21543699, compoundHCID 70977491HCID 70977491, compound

Product 1

HCID 66576768HCID 66576768, compound

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 (0.12 g, 0.48 mmol), the title compound from Example 71 Step C (0.13 g, 0.59 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (6.8 mg, 9.6 μmol), and potassium carbonate (0.200 g, 1.44 mmol) were added tert-butanol (5.3 mL) and water (0.67 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 347.00 [M+H]+; 1H NMR (500 MHz, CD3OD) δ 10.1 (s, 1H), 9.21 (s, 1H), 9.02 (s, 1H), 8.99 (s, 1H), 8.12-8.03 (m, 3H), 3.70 (s, 3H), 3.51-3.48 (m, 2H), 3.41-3.38 (m, 2H), 1.85-1.82 (m, 2H), 1.59-1.56 (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-dd5144ba9fa54717bdec66f201fb892c
Source dataset
uspto-grants-2015_07
Patent number
US09073929B2

Reaction notes

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