Ethanol → HCID 118195137, compound

HRID 923979Notes

Reaction equation

HRID 923979 reaction equation
Br[C:2]1[C:3]([N:22]2[CH2:28][CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[N:29]1[CH:34]=[CH:33][CH:32]=[C:31](B(O)O)[CH:30]=1.C([O-])([O-])=O.[Na+].[Na+].CCO>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[N:22]1([C:3]2[C:2]([C:31]3[CH:30]=[N:29][CH:34]=[CH:33][CH:32]=3)=[CH:21][C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=3)=[O:8])=[CH:5][N:4]=2)[CH2:28][CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 89907953HCID 89907953, compound

Product 1

HCID 118195137HCID 118195137, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 5-bromo-6-(1,4-diazepan-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 145.1, 51 mg, 0.111 mmol), pyridin-3-ylboronic acid (13.6 mg, 0.111 mmol), and Na2CO3 (35 mg, 0.333 mmol) in a mixture of DME (2.4 mL), EtOH (0.32 mL) and water (0.48 mL) was flushed with argon. Pd(PPh3)2Cl2 (4 mg, 0.005 mmol) was added and the mixture was subjected to MW irradiation at 125° C. for 20 min. The vial was cooled to RT and the RM was evaporated to dryness under reduced pressure to give a residue that was triturated with THF and filtered. The filtrate was evaporated to dryness under reduced pressure and the crude product was purified by preparative LC-MS. TFA was removed using a SPE PL-HCO3 (StratoSpheres™) cartridge to afford the title compound. UPLC-MS (Condition 8) tR=1.7 min, m/z=458.1 [M+H]+, m/z=456.2 [M−H]−.

Workup

  1. customwas flushed with argon
  2. customthe mixture was subjected to MW irradiation at 125° C. for 20 min
  3. customthe RM was evaporated to dryness under reduced pressure
  4. customto give a residue that
  5. customwas triturated with THF
  6. filtrationfiltered
  7. customThe filtrate was evaporated to dryness under reduced pressure
  8. customthe crude product was purified by preparative LC-MS
  9. customTFA was removed

Sources & evidence

ORD record
ord-2614ed805a434be99c5328cab56d517d
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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