Potassium Carbonate → HCID 86727595, compound

HRID 519183Notes

Reaction equation

HRID 519183 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[C:16]3[C:25](=[CH:26][C:27]=2Br)[O:24][CH2:23][C:22]2[N:17]3[CH:18]([CH3:38])[C:19](=[O:37])[N:20]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[N:21]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[C:16]3[C:25](=[CH:26][C:27]=2[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=2[F:39])[O:24][CH2:23][C:22]2[N:17]3[CH:18]([CH3:38])[C:19](=[O:37])[N:20]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[N:21]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27343542-Fluorophenylboronic acidHCID 90219620HCID 90219620, compound

Product 1

HCID 86727595HCID 86727595, compoundYield 69.2%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 4-[7-bromo-4-methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-piperazine-1-carboxylic acid tert-butyl ester (0.31 g, 0.508 mmol), (2-fluorophenyl)boronic acid (0.107 g, 0.762 mmol), potassium carbonate (0.140 g, 1.015 mmol) in dioxane (12 mL) and water (2 mL) was added PdCl2(dppf)-CH2Cl2 adduct (0.041 g, 0.051 mmol) and the reaction mixture was heated at 90° C. overnight. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 3-15% EtOAc in petroleum ether) to give 4-[7-(2-fluoro-phenyl)-4-methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-piperazine-1-carboxylic acid tert-butyl ester (0.22 g, 69%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.40 (m, 1H), 7.32 (m, 1H), 7.21-7.09 (m, 2H), 6.95 (s, 1H), 6.61 (s, 1H), 5.19-5.07 (m, 1H), 4.76 (q, J=6.8 Hz, 1H), 4.72-4.57 (d, J=13.2 Hz, 2H), 3.71-3.64 (m, 2H), 3.25 (m, 4H), 2.71 (t, J=4.8 Hz, 4H), 1.52 (d, J=6.8 Hz, 3H), 1.44 (s, 9H), 1.04-0.93 (m, 2H), 0.05-0.02 (m, 9H)

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by column chromatography on silica gel (eluting with 3-15% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-11d5136d4dc04721b171be5430bd7762
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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