Formic Acid → US9321721, Example 1

HRID 631772ノート

反応式

HRID 631772 の反応式
[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:21]=[CH:20][C:19]([C:22]#[C:23][C:24]([NH2:26])=[O:25])=[CH:18][CH:17]=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:21]=[CH:20][C:19](/[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:18][CH:17]=1)=[O:14]

参加物

7

反応物 4

HCID 284Formic AcidHCID 8021DiethylamineHCID 11575IodobenzeneHCID 903870243-{4-[({[2-Fluoro-5-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenyl}prop-2-ynamide

生成物 1

HCID 78426979US9321721, Example 1収率 23.3%

試薬・触媒・溶媒 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
75 °C

実験手順

A mixture of 3-{4-[({[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. After 2 hours, an additional 2 mg bis(dibenzylideneacetone)palladium(0) was added and the reaction continued for 18 hours. The reaction was partitioned between EtOAc and H2O/brine mixture. The EtOAc layer was washed with dilute aqueous HCl, then aqueous Na2CO3, brine, dried with anhydrous Na2SO4 and rotary evaporated. The crude product was chromatographed eluting with EtOAc/CHCl3 and the resulting solid again chromatographed with MeOH/CHCl3 to give the title compound as an off-white solid (8.8 mg, 23%). 1H NMR (Acetone-d6) δ: 8.79 (dd, J=7.5, 2.2 Hz, 1H), 8.43 (d, J=2.9 Hz, 1H), 8.41 (s, 1H), 7.39-7.44 (m, 2H), 7.27-7.39 (m, 7H), 7.11-7.16 (m, 3H), 6.76 (br. s., 1H), 6.49 (s, 1H)

後処理

  1. waitthe reaction continued for 18 hours
  2. customThe reaction was partitioned between EtOAc and H2O/brine mixture
  3. washThe EtOAc layer was washed with dilute aqueous HCl
  4. dry with materialaqueous Na2CO3, brine, dried with anhydrous Na2SO4 and rotary evaporated
  5. customThe crude product was chromatographed
  6. washeluting with EtOAc/CHCl3
  7. customthe resulting solid again chromatographed with MeOH/CHCl3

出典と根拠

ORDレコード
ord-19da11164be84ab9abdcb509922c61ce
出典データセット
uspto-grants-2016_04
特許番号
US09321721B2

反応ノート

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