Water → Methyl 1-(5-(5-ethyl-2-fluorophenyl)pyrimidin-2-yl)-3-(hydroxymethyl)-1H-indole-6-carboxylate

HRID 630539Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].[F:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH3:15])=[CH:10][C:9]=1B(O)O.Br[C:20]1[CH:21]=[N:22][C:23]([N:26]2[C:34]3[C:29](=[CH:30][CH:31]=[C:32]([C:35]([O:37][CH3:38])=[O:36])[CH:33]=3)[C:28]([CH2:39][OH:40])=[CH:27]2)=[N:24][CH:25]=1.O>CC(O)(CC)C>[CH2:14]([C:11]1[CH:12]=[CH:13][C:8]([F:7])=[C:9]([C:20]2[CH:25]=[N:24][C:23]([N:26]3[C:34]4[C:29](=[CH:30][CH:31]=[C:32]([C:35]([O:37][CH3:38])=[O:36])[CH:33]=4)[C:28]([CH2:39][OH:40])=[CH:27]3)=[N:22][CH:21]=2)[CH:10]=1)[CH3:15]

Participants

Conditions

Temperature: 100 °C

Procedure

Potassium carbonate (0.915 g, 6.62 mmol) and 2-fluoro-5-ethylphenylboronic acid (0.742 g, 4.14 mmol) were added at room temperature to a solution 331a) (0.8 g, 2.2 mmol) in 2-methyl-2-butanol 1/water (44 mL, 10:1). The reaction apparatus was set under an argon atmosphere and (Ataphos)2PdCl2 (0.156 g, 0.22 mmol) was introduced. The reaction mixture was stirred at 100° C. for 4 h, cooled to room temperature and filtered through a pad of celite. The filtrate was concentrated and the remnant purified by flash column chromatography [silica; dichloromethane with 1-2% methanol]. White solid. Yield: 0.5 g (56% of theory)

Workup

addition(Ataphos)2PdCl2 (0.156 g, 0.22 mmol) was introduced
temperaturecooled to room temperature
filtrationfiltered through a pad of celite
concentrationThe filtrate was concentrated
customthe remnant purified by flash column chromatography [silica; dichloromethane with 1-2% methanol]

Sources & evidence

ORD record: ord-eb7df7c669f04e7cb5e7cb9f237386b2
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315490B2

Reaction notes

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