Formic Acid → HCID 90386929, compound

HRID 631775Notes

Reaction equation

HRID 631775 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13]([NH:15][C:16]1[CH:17]=[C:18]([C:22]#[C:23][C:24]([NH2:26])=[O:25])[CH:19]=[CH:20][CH:21]=1)=[O:14].I[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(NCC)C.C(O)=O>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:9])[F:10])=[CH:4][C:3]=1[NH:12][C:13]([NH:15][C:16]1[CH:17]=[C:18](/[C:22](/[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:23]\[C:24]([NH2:26])=[O:25])[CH:19]=[CH:20][CH:21]=1)=[O:14]

Participants

7

Reactant 4

HCID 284Formic AcidHCID 8021DiethylamineHCID 11575IodobenzeneHCID 90386939HCID 90386939, compound

Product 1

HCID 90386929HCID 90386929, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 3-{3-[({[2-fluoro-5-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenyl}prop-2-ynamide (31.0 mg, 0.085 mmol), iodobenzene (0.010 mL, 0.089 mmol), diethylamine (0.029 mL, 0.281 mmol), formic acid (0.0083 mL, 0.221 mmol), and bis(dibenzylideneacetone)palladium(0) (3.4 mg, 0.006 mmol) in 1.1 mL EtOAc (degassed) was heated at 75° C. for 16 hours. The reaction was partitioned between EtOAc and H2O/brine mixture. The EtOAc layer was washed with H2O/brine mixture, brine, dried with anhydrous Na2SO4 and rotary evaporated. The crude material was chromatographed eluting with EtOAc/CHCl3 to give the higher Rf material as an off-white solid. The solid was recrystallized from EtOAc/hexane to give the title compound as a white solid (7.5 mg, 20%). 1H NMR (CD3CN) δ: 8.54-8.58 (m, 1H), 7.89 (s, 1H), 7.71 (d, J=3.2 Hz, 1H), 7.14-7.39 (m, 10H), 6.78-6.82 (m, 1H), 6.39 (s, 1H), 6.14 (br. s, 1H), 5.79 (br. s, 1H).

Workup

  1. customThe reaction was partitioned between EtOAc and H2O/brine mixture
  2. washThe EtOAc layer was washed with H2O/brine mixture, brine
  3. dry with materialdried with anhydrous Na2SO4 and rotary evaporated
  4. customThe crude material was chromatographed
  5. washeluting with EtOAc/CHCl3
  6. customto give the higher Rf material as an off-white solid
  7. customThe solid was recrystallized from EtOAc/hexane

Sources & evidence

ORD record
ord-72fafffc786445d5a575cbf9b590cd01
Source dataset
uspto-grants-2016_04
Patent number
US09321721B2

Reaction notes

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