Hydrochloric Acid → N-(azetidin-1-ylsulfonyl)-5-cyclopropyl-2-fluoro-4-((1-(trifluoromethyl)-cyclopentyl)methoxy)benzamide

HRID 1849600ノート

反応式

HRID 1849600 の反応式
[N:1]1([S:5]([NH:8][C:9](=[O:29])[C:10]2[CH:15]=[C:14](Cl)[C:13]([O:17][CH2:18][C:19]3([C:24]([F:27])([F:26])[F:25])[CH2:23][CH2:22][CH2:21][CH2:20]3)=[CH:12][C:11]=2[F:28])(=[O:7])=[O:6])[CH2:4][CH2:3][CH2:2]1.[CH:30]1(B(O)O)[CH2:32][CH2:31]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].F[B-](F)(F)F.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.Cl>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:1]1([S:5]([NH:8][C:9](=[O:29])[C:10]2[CH:15]=[C:14]([CH:30]3[CH2:32][CH2:31]3)[C:13]([O:17][CH2:18][C:19]3([C:24]([F:27])([F:26])[F:25])[CH2:23][CH2:22][CH2:21][CH2:20]3)=[CH:12][C:11]=2[F:28])(=[O:7])=[O:6])[CH2:4][CH2:3][CH2:2]1

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 86703454N-(azetidin-1-ylsulfonyl)-5-chloro-2-fluoro-4-((1-(trifluoromethyl)-cyclopentyl)methoxy)benzamide

生成物 1

HCID 86703455N-(azetidin-1-ylsulfonyl)-5-cyclopropyl-2-fluoro-4-((1-(trifluoromethyl)-cyclopentyl)methoxy)benzamide収率 61%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

To a mixture of N-(azetidin-1-ylsulfonyl)-5-chloro-2-fluoro-4-((1-(trifluoromethyl)-cyclopentyl)methoxy)benzamide (0.18 g, 0.39 mmol), cyclopropylboronic acid (0.40 g, 4.65 mmol) and potassium phosphate (2.55 g, 12.00 mmol) in toluene (20 mL) and water (1.0 mL) was sparged with a nitrogen atmosphere for 10 minutes, tricyclohexylphosphine tetrafluoroborate (0.17 g, 0.48 mmol) and palladium acetate (0.05 g, 0.22 mmol) was added to this reaction mixture. The reaction mixture was heated to 100° C. for 96 hours under a nitrogen atmosphere and then cooled to ambient temperature. 5% aqueous hydrochloric acid (20 mL) was added and the mixture was extracted with ethyl acetate (100 mL×3), the combined organics were washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (10% to 30% gradient ethyl acetate in hexanes) afforded the title compound (0.11 g, 61%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 8.63 (d, J=16.2 Hz, 1H), 7.62 (d, J=9.0 Hz, 1H), 6.57 (d, J=14.1 Hz, 1H), 4.23 (t, J=7.5 Hz, 4H), 3.99 (s, 2H), 2.31-2.20 (m, 2H), 2.08-1.94 (m, 3H), 1.89-1.70 (m, 6H), 0.95-0.88 (m, 2H), 0.67-0.60 (m, 2H); MS (ES+) m/z 465.1 (M+1), MS (ES−) m/z 463.1 (M−1).

後処理

  1. customwas sparged with a nitrogen atmosphere for 10 minutes
  2. temperaturecooled to ambient temperature
  3. extractionthe mixture was extracted with ethyl acetate (100 mL×3)
  4. washthe combined organics were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by column chromatography (10% to 30% gradient ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-893782fbdf084b4bba2f612298247e1d
出典データセット
uspto-grants-2015_02
特許番号
US08952169B2

反応ノート

読み込み中…