Water → HCID 72203012, compound

HRID 629063Notes

Reaction equation

HRID 629063 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[CH3:22])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1)=[O:6].[CH3:23][O:24][C:25]1[N:30]=[CH:29][C:28](B(O)O)=[CH:27][N:26]=1.C([O-])([O-])=O.[Na+].[Na+].O>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.COCCOC.CCO>[CH3:23][O:24][C:25]1[N:30]=[CH:29][C:28]([C:2]2[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=2[CH3:22])[C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=2)=[O:6])=[CH:27][N:26]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27367782-Methoxypyrimidine-5-boronic acidHCID 89907516HCID 89907516, compound

Product 1

HCID 72203012HCID 72203012, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

3-Iodo-4-methyl-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 13.1, 84 mg, 0.2 mmol), 2-methoxypyrimidin-5-ylboronic acid (61.6 mg, 0.4 mmol), Na2CO3 (63.6 mg, 0.600 mmol), Pd(PPh3)2Cl2 (7.02 mg, 10.00 μmol), water (200 μL), EtOH (133 μL) and DME (1 mL) were added to a vial, which was sealed, evacuated/purged with argon and subjected to MW irradiation at 125° C. for 20 min The RM was diluted with THF (1 mL) and stirred with Si-Thiol (69.4 mg, 0.100 mmol) for a 2 h. The filtrate was evaporated to dryness under reduced pressure to give the crude product which was purified by flash chromatography (Silica gel column, 4 g, DCM/MeOH+1% NH4OH, gradient from 1% to 15% MeOH+1% NH4OH) to afford the title compound as a beige solid. UPLC-MS (Condition 1) tR=2.89 min, m/z=404.1 [M+H]+, m/z=402.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.35 (s, 3H) 3.99 (s, 3H) 7.37 (d, J=8.6 Hz, 2H) 7.52 (d, J=8.1 Hz, 1H) 7.88 (d, J=9.3 Hz, 2H), 7.90 (br. s, br. s, 1H) 7.93 (dd, 1H) 8.74 (s, 2H) 10.36 (s, 1H).

Workup

  1. customwas sealed
  2. customevacuated/purged with argon
  3. customsubjected to MW irradiation at 125° C. for 20 min The RM
  4. additionwas diluted with THF (1 mL)
  5. customThe filtrate was evaporated to dryness under reduced pressure
  6. customto give the crude product which
  7. customwas purified by flash chromatography (Silica gel column, 4 g, DCM/MeOH+1% NH4OH, gradient from 1% to 15% MeOH+1% NH4OH)

Sources & evidence

ORD record
ord-5a14c00021684c09aa26343f44b7aee5
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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