1,2-Dimethoxyethane → HCID 57732429, compound

HRID 1365071Notes

Reaction equation

HRID 1365071 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:16])=[C:6]([C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:9])[CH:7]=1.CC1(C)C(C)(C)OB([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[NH:30][N:29]=[CH:28]3)O1.C(COC)OC.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)C>[F:16][C:5]1[CH:4]=[CH:3][C:2]([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[NH:30][N:29]=[CH:28]3)=[CH:7][C:6]=1[C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:9]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 177504691H-Indazole-5-boronic acid pinacol esterHCID 43160375HCID 43160375, compound

Product 1

HCID 57732429HCID 57732429, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
150 °C

Procedure

The following reagents were mixed in no particular order and heated to 150° C. in a microwave for 1000 seconds: (5-bromo-2-fluorophenyl)(phenyl)methanone (from example 9, step 1) (278 mg, 1.0 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (486 mg, 2.0 mmol), dichlorobis(triphenyl-phosphine)palladium(II) (70 mg, 0.10 mmol), dimethoxyethane (2 mL), ethanol (1 mL) and a 2M aqueous solution of sodium carbonate (1 mL, 2.0 mmol). The reaction mixture was then filtered through a plug of celite, rinsed with methanol and concentrated to dryness. Purification from silica gel eluting with a 50% solution of ethyl acetate and hexanes affords [2-fluoro-5-(1H-indazol-5-yl)phenyl](phenyl)methanone (187 mg, 0.6 mmol) 1H NMR (400 MHz, DMSO-D6) δ ppm 13.1 (s, 1 H) 8.1 (s, 1 H) 8.1 (s, 1 H) 8.0 (m, J=5.9 Hz, 1 H) 7.8 (m, J=7.5 Hz, 3 H) 7.7 (m, 2 H) 7.6 (m, 3 H) 7.5 (dd, J=9.1, 9.1 Hz, 1 H)

Workup

  1. additionThe following reagents were mixed in no particular order
  2. filtrationThe reaction mixture was then filtered through a plug of celite
  3. washrinsed with methanol
  4. concentrationconcentrated to dryness
  5. customPurification from silica gel eluting with a 50% solution of ethyl acetate and hexanes

Sources & evidence

ORD record
ord-10833e5d01494960aa04b05248de22f7
Source dataset
uspto-grants-2011_02
Patent number
US07888503B2

Reaction notes

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