tert-Butanol → HCID 89961736, compound

HRID 1521602Notes

Reaction equation

HRID 1521602 reaction equation
[CH3:1][C:2]1[N:6]2[C:7]3[C:12]([CH2:13][CH2:14][C:5]2=[N:4][N:3]=1)=[CH:11][C:10](B1OC(C)(C)C(C)(C)O1)=[CH:9][CH:8]=3.Br[C:25]1[CH:26]=[N:27][CH:28]=[C:29]([C:31]([C:34]2[O:35][C:36]([CH:39]3[CH2:41][CH2:40]3)=[N:37][N:38]=2)([CH3:33])[CH3:32])[CH:30]=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:39]1([C:36]2[O:35][C:34]([C:31]([C:29]3[CH:30]=[C:25]([C:10]4[CH:11]=[C:12]5[C:7](=[CH:8][CH:9]=4)[N:6]4[C:2]([CH3:1])=[N:3][N:4]=[C:5]4[CH2:14][CH2:13]5)[CH:26]=[N:27][CH:28]=3)([CH3:33])[CH3:32])=[N:38][N:37]=2)[CH2:41][CH2:40]1

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 11430Potassium CarbonateHCID 70977989HCID 70977989, compoundHCID 89961654HCID 89961654, compound

Product 1

HCID 89961736HCID 89961736, 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 53 Step J (0.025 g, 0.080 mmol), the title compound from Example 70 Step A (0.025 g, 0.080 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (1.1 mg, 1.6 μmol), and potassium carbonate (0.033 g, 0.241 mmol) were added tert-butanol (0.89 mL) and water (0.11 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 afford the title compound: LCMS m/z 413.02 [M+H]+; 1H NMR (500 MHz, CD3OD) δ 8.90 (s, 1H), 8.64 (s, 1H), 8.30 (s, 1H), 7.90-7.81 (m, 3H), 3.22 (s, 4H), 2.90 (s, 3H), 2.20-2.14 (m, 1H), 1.92 (s, 6H), 1.18-1.16 (m, 2H), 1.07-1.04 (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-c4aed0591d834211ac54ddd5b4e0a4d7
Source dataset
uspto-grants-2015_07
Patent number
US09073929B2

Reaction notes

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