Formic Acid → US9321721, Example 2

HRID 631773ノート

反応式

HRID 631773 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:29]=[C:30]([O:34][CH3:35])[CH:31]=[CH:32][CH:33]=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]=[C:30]([O:34][CH3:35])[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 69839Benzene, 1-iodo-3-methoxy-HCID 903870243-{4-[({[2-Fluoro-5-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenyl}prop-2-ynamide

生成物 1

HCID 78427115US9321721, Example 2収率 30%

試薬・触媒・溶媒 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒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), 3-iodoanisole (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 1.4 mL EtOAc (degassed) was heated at 75° C. for 17 hours. The reaction was partitioned between EtOAc and H2O/brine mixture. The EtOAc layer was washed with dilute aqueous HCl, then aqueous NaHCO3, brine, and dried with anhydrous Na2SO4 to give 20 mL of EtOAc solution of crude material. The EtOAc solution was filtered past a plug of silica gel eluting with EtOAc, evaporated, and the resulting solid chromatographed eluting with CHCl3/MeOH to give the title compound as a light tan solid (12.0 mg, 30%). 1H NMR (Acetone-d6) δ: 8.80 (d, J=5.9 Hz, 1H), 8.46 (s, 1H), 8.42 (d, J=2.6 Hz, 1H), 7.33-7.47 (m, 4H), 7.23-7.29 (m, 1H), 7.15 (d, J=8.5 Hz, 2H), 6.91-7.00 (m, 2H), 6.82-6.87 (m, 2H), 6.65 (br. s., 1H), 6.47 (s, 1H), 3.77 (s, 3H).

後処理

  1. customThe reaction was partitioned between EtOAc and H2O/brine mixture
  2. washThe EtOAc layer was washed with dilute aqueous HCl
  3. dry with materialaqueous NaHCO3, brine, and dried with anhydrous Na2SO4
  4. customto give 20 mL of EtOAc solution of crude material
  5. filtrationThe EtOAc solution was filtered past a plug of silica gel eluting with EtOAc
  6. customevaporated
  7. customthe resulting solid chromatographed
  8. washeluting with CHCl3/MeOH

出典と根拠

ORDレコード
ord-cbd6507b896e4ea195d921b89f63ccc2
出典データセット
uspto-grants-2016_04
特許番号
US09321721B2

反応ノート

読み込み中…