Sodium Carbonate → HCID 89649188, compound

HRID 2207676Notes

Reaction equation

HRID 2207676 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([F:13])=[C:8](B(O)O)[CH:9]=1)[CH3:2].Br[C:15]1[C:20]([CH2:21][CH3:22])=[CH:19][N:18]=[C:17]([C@H:23]2[CH2:27][CH2:26][C@@:25]3([CH2:31][CH2:30][N:29]([CH3:32])[C:28]3=[O:33])[NH:24]2)[CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+]>CC#N.O.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([F:13])=[C:8]([C:15]2[C:20]([CH2:21][CH3:22])=[CH:19][N:18]=[C:17]([C@H:23]3[CH2:27][CH2:26][C@@:25]4([CH2:31][CH2:30][N:29]([CH3:32])[C:28]4=[O:33])[NH:24]3)[CH:16]=2)[CH:9]=1)[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 162174685-Ethoxy-2-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 89649496HCID 89649496, compound

Product 1

HCID 89649188HCID 89649188, compoundYield 74.4%

Reagents, catalysts & solvents 3

HCID 178419050HCID 178419050, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
140 °C

Procedure

To a microwave vial containing a solution of (5-ethoxy-2-fluoro-phenyl)boronic acid (54.39 mg, 0.3000 mmol) in MeCN (1 mL) and water (0.2000 mL) was added (2R,5S)-2-(4-bromo-5-ethyl-2-pyridyl)-7-methyl-1,7-diazaspiro[4.4]nonan-6-one (which may be prepared as described in Description 122) (80 mg, 0.2400 mmol), sodium carbonate (50.12 mg, 0.4700 mmol) and bis(triphenylphosphine)palladium (II) dichloride (8.2 mg, 0.0100 mmol). The microwave vial was sealed and heated at 140° C. for 15 minutes. The reaction was concentrated in vacuo and loaded onto a silica column (10 g, Biotage SNAP cartridge). The silica column was then eluted with a gradient of (80:20:2 EtOAc:MeOH:0.88M NH3):EtOAc from 0% to 100%. Fractions containing desired product were combined and concentrated in vacuo to give (2R,5S)-2-[4-(5-ethoxy-2-fluoro-phenyl)-5-ethyl-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one (69.9 mg, 0.1759 mmol, 74.4% yield) as a colourless oil;

Workup

  1. customThe microwave vial was sealed
  2. concentrationThe reaction was concentrated in vacuo
  3. washThe silica column was then eluted with a gradient of (80:20:2 EtOAc:MeOH:0.88M NH3)
  4. additionFractions containing desired product
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5263a05cf6b54e29be393f110b9c43a7
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

Loading…