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Tris(furan-2-yl)phosphane → 2,2-Difluoro-N-[(1S,2R)-1-fluoromethyl-2-hydroxy-2-(4-{6-[(methanesulfonyl-methoxy-amino)-methyl]-pyridin-3-yl}-phenyl)-ethyl]-acetamide

HRID 525539
ノート
印刷プレビュー

反応式

HRID 525539 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]([O:14][CH3:15])[S:10]([CH3:13])(=[O:12])=[O:11])=[N:6][CH:7]=1.[F:16][CH:17]([F:36])[C:18]([NH:20][C@H:21]([CH2:34][F:35])[C@H:22]([OH:33])[C:23]1[CH:28]=[CH:27][C:26]([Sn](C)(C)C)=[CH:25][CH:24]=1)=[O:19].O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>CN1CCCC1=O.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:16][CH:17]([F:36])[C:18]([NH:20][C@H:21]([CH2:34][F:35])[C@H:22]([OH:33])[C:23]1[CH:24]=[CH:25][C:26]([C:2]2[CH:7]=[N:6][C:5]([CH2:8][N:9]([S:10]([CH3:13])(=[O:12])=[O:11])[O:14][CH3:15])=[CH:4][CH:3]=2)=[CH:27][CH:28]=1)=[O:19]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 521585Tris(furan-2-yl)phosphaneHCID 866954252,2-Difluoro-N-[(1S,2R)-1-fluoromethyl-2-hydroxy-2-(4-trimethylstannanyl-phenyl)-ethyl]-acetamideHCID 86695426N-(5-Bromo-pyridin-2-ylmethyl)-N-methoxy-methane sulfonamide

生成物 1

HCID 866954272,2-Difluoro-N-[(1S,2R)-1-fluoromethyl-2-hydroxy-2-(4-{6-[(methanesulfonyl-methoxy-amino)-methyl]-pyridin-3-yl}-phenyl)-ethyl]-acetamide収率 16%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
80 °C

実験手順

To a stirred solution of N-(5-Bromo-pyridin-2-ylmethyl)-N-methoxy-methane sulfonamide (0.2 g, 0.678 mmol) in N-Methyl-2-pyrrolidone (8 mL) is added and 2,2-Difluoro-N-[(1S,2R)-1-fluoromethyl-2-hydroxy-2-(4-trimethylstannanyl-phenyl)ethyl]acetamide (0.27 g, 0.678 mmol). Reaction mixture is degassed with nitrogen for 15 minutes then added tris(dibenzylideneacetone)dipalladium(0) (0.06 mg, 0.068 mmol) and Tri-2-furylphosphine (0.03 g, 0.136 mmol) simultaneously. The resulting reaction mixture is stirred at 80° C. for 5 hours. Diluted with water and extracted with ethyl acetate. Organic layer is dried over sodium sulphate, solvent is evaporated in vacuo and purified by combi-flash using 50% ethyl acetate in hexane as an eluent to afford the title compound (0.05 g). 1HNMR (400 MHz, DMSO-d6) δ: 3.16 (s, 3H), 3.49 (s, 3H), 4.30-4.37 (m, 1.5H), 4.41-4.46 (m, 0.5H), 4.46 (s, 2H), 4.54-4.56 (m, 0.5H), 4.65-4.68 (m, 0.5H), 4.89 (m, 1H), 5.94 (d, J=4.2 Hz, 1H), 6.20 (t, J=53.76 Hz, 1H), 7.47 (d, J=8.2 Hz, 2H), 7.59 (d, J=8.16 Hz, 1H), 7.74 (d, J=8.2 Hz, 2H), 8.14-8.16 (dd, J1=2.32 Hz, J2=8.16 Hz, 1H), 8.86 (d, J=8.72 Hz, 1H), 8.91 (d, J=2.08 Hz, 1H). LCMS (m/z): [M+H]=461.9.

後処理

  1. customReaction mixture
  2. customis degassed with nitrogen for 15 minutes
  3. customThe resulting reaction mixture
  4. extractionextracted with ethyl acetate
  5. dry with materialOrganic layer is dried over sodium sulphate, solvent
  6. customis evaporated in vacuo
  7. custompurified by combi-flash

出典と根拠

ORDレコード
ord-56cbe1237c3846949222aad271b8706b
出典データセット
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09340564B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート