Sodium Carbonate → HCID 86711410, compound

HRID 926338Notes

Reaction equation

HRID 926338 reaction equation
[CH:1]1([C:4]2[N:8]=[CH:7][N:6]([C:9]3[CH:32]=[C:14]4[C:15]5[C:20]([CH2:21][CH2:22][N:13]4[C:12](=[O:33])[CH2:11][N:10]=3)=[C:19](B3OC(C)(C)C(C)(C)O3)[CH:18]=[CH:17][CH:16]=5)[N:5]=2)[CH2:3][CH2:2]1.Br[C:35]1[CH:40]=[CH:39][C:38]([F:41])=[CH:37][N:36]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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]>[CH:1]1([C:4]2[N:8]=[CH:7][N:6]([C:9]3[CH:32]=[C:14]4[C:15]5[C:20]([CH2:21][CH2:22][N:13]4[C:12](=[O:33])[CH2:11][N:10]=3)=[C:19]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][N:36]=3)[CH:18]=[CH:17][CH:16]=5)[N:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27831712-Bromo-5-fluoropyridineHCID 86711411HCID 86711411, compound

Product 1

HCID 86711410HCID 86711410, compoundYield 21.8%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Example 133. A suspension of 2-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one (95 mg, 0.21 mmol), 2-bromo-5-fluoropyridine (79 mg, 0.45 mmol) and PdCl2(dppf)*CH2Cl2 (17 mg, 0.021 mmol) in DME (2.1 mL) was treated with a 2M aq. solution of Na2CO3 (0.5 mL, 1.06 mmol). The mixture was heated to 80° C. for 13 h, the allowed to cool to RT and poured onto H2O. The mixture was extracted with DCM and the combined org. layers were washed with brine, dried over over Na2SO4, filtered and concentrated in vacuo. Purification by SFC (Column: Silica 5 μm, 250×30 mm, Princeton; isocratic 5% MeOH/CO2 for 20 min; flow 100 mL/min) gave the title compound (19 mg). UPLC-MS: MS 415.2 (M+H+); UPLC rt 1.02 min. 1H NMR (600 MHz, DMSO-d6): δ ppm 0.71-0.90 (m, 2H); 0.90-1.00 (m, 2H); 1.91-2.09 (m, 1H); 2.91-3.09 (m, 2H); 3.73 (t, J=6.24 Hz, 2H); 4.33 (s, 2H); 7.06 (s, 1H); 7.40-7.56 (m, 1H); 7.66 (d, J=7.70 Hz, 1H); 7.73 (dd, J=8.71, 4.68 Hz, 1H); 7.83-8.01 (m, 2H); 8.73 (d, J=2.75 Hz, 1H); 9.03 (s, 1H).

Workup

  1. temperatureto cool to RT
  2. additionpoured onto H2O
  3. extractionThe mixture was extracted with DCM
  4. washlayers were washed with brine
  5. dry with materialdried over over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by SFC (Column: Silica 5 μm, 250×30 mm, Princeton; isocratic 5% MeOH/CO2 for 20 min; flow 100 mL/min)

Sources & evidence

ORD record
ord-3c15eb7638ee4afb8b9f06e3cbab0ca1
Source dataset
uspto-grants-2016_03
Patent number
US09284331B2

Reaction notes

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