Dichloromethane → HCID 71042771, compound

HRID 1501881Notes

Reaction equation

HRID 1501881 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2([C:36]#[N:37])[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[C:16]4[CH:35]=[CH:34][CH:33]=[CH:32][C:17]=4[C:18]4[CH2:19][N:20]([C@H:25]5[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]5[OH:31])[C:21](=[O:24])[C:22]=4[CH:23]=3)[CH2:10][CH2:9]2)[CH:5]=[CH:4][CH:3]=1.[CH3:38]B(O)O.C(=O)([O-])[O-].[K+].[K+].ClCCl>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].O1CCOCC1.O>[OH:31][C@H:26]1[CH2:27][CH2:28][CH2:29][CH2:30][C@@H:25]1[N:20]1[CH2:19][C:18]2[C:17]3[CH:32]=[CH:33][CH:34]=[CH:35][C:16]=3[C:15]([CH2:14][N:11]3[CH2:12][CH2:13][C:8]([C:6]4[CH:5]=[CH:4][CH:3]=[C:2]([CH3:38])[N:7]=4)([C:36]#[N:37])[CH2:9][CH2:10]3)=[CH:23][C:22]=2[C:21]1=[O:24]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 139377Methylboronic AcidHCID 71467812HCID 71467812, compound

Product 1

HCID 71042771HCID 71042771, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

To a solution of 4-(6-chloropyridin-2-yl)-1-({2-[(1S,2S)-2-hydroxycyclohexyl]-3-oxo-2,3-dihydro-1H-benzo[e]isoindol-5-yl}methyl)piperidine-4-carbonitrile (0.050 g, 0.097 mmol) in 1 mL mixture of 1,4-dioxane:water (10:1) under an atmosphere of nitrogen was added methylboronic acid (7.0 mg, 0.12 mmol), potassium carbonate (0.040 g, 0.29 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloro-palladium(II), 1:1 complex with dichloromethane (1.4 mg, 0.0019 mmol). The mixture was irradiated in a microwave reactor at 125° C. for 1 hr, cooled to ambient temperature and extracted 2× with dichloromethane. The combined organic extracts were dried with magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified via preparative reverse phase HPLC to provide the titled compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 495.2765 for [M+H]+[calc'd for C31H35N4O2, [M+H]+=495.2755]: 1H NMR (400 MHz, CDCl3) δ 8.35-8.33 (m, 1H), 7.88-7.85 (m, 1H), 7.76 (s, 1H), 7.66-7.54 (m, 3H), 7.34-7.32 (m, 1H), 7.07-7.04 (m, 1H), 4.84-4.68 (m, 2H), 4.20-4.14 (m, 1H), 3.98-3.79 (m, 2H), 3.77-3.74 (m, 1H), 3.02-2.96 (m, 1H), 2.63-2.55 (m, 1H), 2.52 (s, 3H), 2.36-2.21 (m, 2H), 2.06-1.97 (m, 2H), 1.90-1.82 (m, 1H), 1.70-1.25 (m, 6H), 0.97-0.83 (m, 3H) ppm.

Workup

  1. customThe mixture was irradiated in a microwave reactor at 125° C. for 1 hr
  2. extractionextracted 2× with dichloromethane
  3. dry with materialThe combined organic extracts were dried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified via preparative reverse phase HPLC

Sources & evidence

ORD record
ord-efdf3a6886c24a57863f8c2092c6da0e
Source dataset
uspto-grants-2015_12
Patent number
US09206200B2

Reaction notes

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