Sodium Carbonate → HCID 73334762, compound

HRID 532966Notes

Reaction equation

HRID 532966 reaction equation
[CH:1]1([C:4]2[N:5]=[CH:6][N:7]([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)[CH:8]=2)[CH2:3][CH2:2]1.Br[C:35]1[CH:40]=[N:39][C:38]([F:41])=[CH:37][N:36]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:1]1([C:4]2[N:5]=[CH:6][N:7]([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]=[N:39][C:38]([F:41])=[CH:37][N:36]=3)[CH:18]=[CH:17][CH:16]=5)[CH:8]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 665211912-Bromo-5-fluoropyrazineHCID 86711413HCID 86711413, compound

Product 1

HCID 73334762HCID 73334762, compoundYield 61.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

Example 137. A suspension of 2-(4-cyclopropyl-1H-imidazol-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 (100 mg, 0.225 mmol), 2-bromo-5-fluoropyrazine (90 mg, 0.51 mmol) and Pd(PPh3)4 (39 mg, 0.034 mmol) in DME (2.8 mL) was treated with a 2M aq. solution of Na2CO3 (0.6 mL, 1.12 mmol). The mixture was heated to 90° C. for 2 h, 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 Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash-column chromatography over silicagel (Biotage Isolera Four, eluent: 25% EtOAc in heptane for 2 min, then from 25% EtOAc in heptane to 100% EtOAc in heptane in 10 min, 100% EtOAc in heptane for 5 min) to yield a solid which was crystallized from diethyl ether and afforded the title compound (57 mg). UPLC-MS: MS 415.2 (M-FH+); UPLC rt 0.92 min. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.59-0.69 (m, 2 H), 0.72-0.82 (m, 2 H), 1.75-1.86 (m, 1 H), 2.97 (t, J=5.62 Hz, 2 H), 3.70 (t, J=6.11 Hz, 2 H), 4.24 (br. s., 2 H), 7.15 (s, 1 H), 7.43 (s, 1 H), 7.54 (t, J=7.82 Hz, 1 H), 7.69 (d, J=7.58 Hz, 1 H), 8.01-8.16 (m, 2 H), 8.58 (s, 1 H), 8.83 (d, J=8.31 Hz, 1 H).

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 Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash-column chromatography over silicagel (Biotage Isolera Four, eluent
  9. waitfrom 25% EtOAc in heptane to 100% EtOAc in heptane in 10 min
  10. custom100% EtOAc in heptane for 5 min) to yield a solid which
  11. customwas crystallized from diethyl ether

Sources & evidence

ORD record
ord-fb929bc0144b478896e0931587d29738
Source dataset
uspto-grants-2014_10
Patent number
US08853203B2

Reaction notes

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