4-Phenoxyphenylboronic acid → HCID 178501053, compound

HRID 449054Notes

Reaction equation

HRID 449054 reaction equation
[CH3:1][O:2][C:3]([C@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]2[N:15]3[CH:16]=[CH:17][N:18]=[C:19]([NH2:20])[C:14]3=[C:13](Br)[N:12]=2)[CH2:7][CH2:6]1)=[O:4].[O:22]([C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.O.O.[F-].[K+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]([C@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]2[N:15]3[CH:16]=[CH:17][N:18]=[C:19]([NH2:20])[C:14]3=[C:13]([C:32]3[CH:33]=[CH:34][C:29]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:30][CH:31]=3)[N:12]=2)[CH2:7][CH2:6]1)=[O:4]

Participants

7

Reactant 3

HCID 27343774-Phenoxyphenylboronic acidHCID 23708904Potassium fluoride dihydrateHCID 178501044HCID 178501044, compound

Product 1

HCID 178501053HCID 178501053, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred mixture of trans-4-(8-amino-1-bromo-imidazo[1,5-a]pyrazin-3-yl)-cyclohexanecarboxylic acid methyl ester (2.00 g, 5.66 mmol) and 4-phenoxyphenylboronic acid (1.454 g, 6.7 mmol) in DME (25.00 mL) and H2O (8.3 mL) was added potassium fluoride dihydrate (1.865 g, 19.82 mmol). The mixture was bubbled with nitrogen for 5 min before Pd(PPh3)4 (330 mg, 0.28 mmol) was added to. The resulting mixture was refluxed overnight at 100° C. Solvent was removed under reduced pressure and the product was purified by flash chromatography (2% MeOH in DCM). 1H NMR (400 MHz, CD3OD) δ 1.59-1.87 (m, 4H), 2.02-2.18 (m, 4H), 2.41-2.53 (m, 1H), 3.09-3.19 (m, 1H), 3.68 (s, 3H), 6.94-7.20 (m, 6H), 7.32-7.44 (m, 2H), 7.52-7.63 (m, 3H). MS (ES+): m/z: 442.97 [MH+]. HPLC: tR=2.48 min (OpenLynx: polar—5 min).

Workup

  1. additionwas added to
  2. customSolvent was removed under reduced pressure
  3. customthe product was purified by flash chromatography (2% MeOH in DCM)
  4. customHPLC: tR=2.48 min (OpenLynx: polar—5 min)

Sources & evidence

ORD record
ord-835b5df35c9044c693cd352bd7f923c4
Source dataset
uspto-grants-2013_07
Patent number
US08481733B2

Reaction notes

Loading…