Diisopropylethylamine → (E)-N-{(S)-2-[4-(4-Fluoro-benzoyl)-piperidin-1-yl]-1-hydroxymethyl-ethyl)-3-(5-cyano-2-methoxy-phenyl)-acrylamide

HRID 434304ノート

反応式

HRID 434304 の反応式
Cl.[NH2:2][C@H:3]([CH2:20][OH:21])[CH2:4][N:5]1[CH2:10][CH2:9][CH:8]([C:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[O:12])[CH2:7][CH2:6]1.C(N(C(C)C)CC)(C)C.[C:31]([C:33]1[CH:34]=[CH:35][C:36]([O:44][CH3:45])=[C:37](/[CH:39]=[CH:40]/[C:41](O)=[O:42])[CH:38]=1)#[N:32].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>ClCCl>[F:19][C:16]1[CH:15]=[CH:14][C:13]([C:11]([CH:8]2[CH2:7][CH2:6][N:5]([CH2:4][C@H:3]([NH:2][C:41](=[O:42])/[CH:40]=[CH:39]/[C:37]3[CH:38]=[C:33]([C:31]#[N:32])[CH:34]=[CH:35][C:36]=3[O:44][CH3:45])[CH2:20][OH:21])[CH2:10][CH2:9]2)=[O:12])=[CH:18][CH:17]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11458357(E)-3-(5-cyano-2-methoxy-phenyl)-acrylic acidHCID 68809497[1-((S)-2-Amino-3-hydroxy-propyl)-piperidin-4-yl]-(4-fluoro-phenyl)-methanone hydrochloride

生成物 1

HCID 69986033(E)-N-{(S)-2-[4-(4-Fluoro-benzoyl)-piperidin-1-yl]-1-hydroxymethyl-ethyl)-3-(5-cyano-2-methoxy-phenyl)-acrylamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of [1-((S)-2-amino-3-hydroxy-propyl)-piperidin-4-yl]-(4-fluoro-phenyl)-methanone hydrochloride (1.8 g, 5.7 mmol) and diisopropylethylamine (2.0 ml, 11.4 mmol) in dichloromethane (45 ml) is added (E)-3-(5-cyano-2-methoxy-phenyl)-acrylic acid (1.1 g, 5.7 mmol) followed by 2-(1H benzotriazol-1-yl)-1,1,3,3,-tetramethyluronium tetrafluoroborate (1.83 g, 5.7 mmol). The reaction mixture is stirred at ambient temperature for 4.5 hours, then filtered and the filtrate washed with water (50 ml), saturated sodium bicarbonate solution (50 ml), water (50 ml) and brine (50 ml). The organic phase is dried over magnesium sulphate, the solvent evaporated and the residue purified by flash silica chromatography (dichloromethane:methanol; 98:2 to 92:8 elution gradient) to afford the product, [MH]+466.1.

後処理

  1. filtrationfiltered
  2. washthe filtrate washed with water (50 ml), saturated sodium bicarbonate solution (50 ml), water (50 ml) and brine (50 ml)
  3. dry with materialThe organic phase is dried over magnesium sulphate
  4. customthe solvent evaporated
  5. customthe residue purified by flash silica chromatography (dichloromethane:methanol; 98:2 to 92:8 elution gradient)
  6. customto afford the product, [MH]+466.1

出典と根拠

ORDレコード
ord-027795b7f3a748158af9e2b8b8b6ecbc
出典データセット
uspto-grants-2003_12
特許番号
US06670379B2

反応ノート

読み込み中…