Diisopropylethylamine → 2-(4-Chloro-5-methyl-3-oxazol-2-yl-pyrazol-1-yl)-1-[4-(4-fluoro-benzyl)-4-hydroxy-piperidin-1-yl]-ethanone

HRID 2103416ノート

反応式

HRID 2103416 の反応式
[F:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][C:7]2([OH:13])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[Cl:16][C:17]1[C:18]([C:27]2[O:28][CH:29]=[CH:30][N:31]=2)=[N:19][N:20]([CH2:23][C:24](O)=[O:25])[C:21]=1[CH3:22].F[P-](F)(F)(F)(F)F.N1([PH+](N2CCCC2)N2CCCC2)CCCC1.CCN(C(C)C)C(C)C>CC(N(C)C)=O.CCOC(C)=O>[Cl:16][C:17]1[C:18]([C:27]2[O:28][CH:29]=[CH:30][N:31]=2)=[N:19][N:20]([CH2:23][C:24]([N:10]2[CH2:9][CH2:8][C:7]([CH2:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:15][CH:14]=3)([OH:13])[CH2:12][CH2:11]2)=[O:25])[C:21]=1[CH3:22]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 104886244-[(4-Fluorophenyl)methyl]piperidin-4-olHCID 22226026Tripyrrolidinophosphonium hexafluorophosphateHCID 59813981(4-Chloro-5-methyl-3-oxazol-2-yl-pyrazol-1-yl)-acetic acid

生成物 1

HCID 160485492-(4-Chloro-5-methyl-3-oxazol-2-yl-pyrazol-1-yl)-1-[4-(4-fluoro-benzyl)-4-hydroxy-piperidin-1-yl]-ethanone収率 30.2%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 31374Dimethylacetamide溶媒

実験手順

To a 20 mL vial equipped with a magnetic stirring bar was added 63 mg of 4-(4-Fluoro-benzyl)-piperidin-4-ol (0.3 mmol, 1.2 equiv.), 62 mg of (4-Chloro-5-methyl-3-oxazol-2-yl-pyrazol-1-yl)-acetic acid (0.26 mmol, 1.0 equiv), and 138 mg of benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (0.27 mmol, 1.0 equiv). The reagents were dissolved in 0.6 mL of DMA and to the resultant solution was added 0.18 mL of DIPEA (1.0 mmol, 3.8 equiv.). The reaction solution was stirred for 14 h and then poured into 50 mL of EtOAc. The organic extracts were washed with saturated aq. NaCl (5×10 mL), 1% aq NaOH (1×10 mL), and 0.1 N HCl (1×10 mL). The organic extracts were dried over MgSO4 and concentrated in vacuo to afford a yellow oil, which was purified by preparative HPLC to afford 34 mg of 2-(4-Chloro-5-methyl-3-oxazol-2-yl-pyrazol-1-yl)-1-[4-(4-fluoro-benzyl)-4-hydroxy-piperidin-1-yl]-ethanone (30% yield): MS (ES) M+H expected=413.2, found 413.2. 1H NMR (CDCl3, 400 MHz, 23° C.) δ 7.69 (s, 1H), 7.27 (s, 1H), 7.11-7.14 (m, 2H), 6.98-7.03 (m, 2H), 5.06 (d, J=16.0 Hz, 1H), 4.93 (d, J=16.0 Hz, 1H), 4.32-4.35 (m, 1H), 3.66-3.69 (m, 1H), 3.43-3.50 (m, 1H), 2.96-3.03 (m, 1H), 2.74 (s, 2H), 2.30 (s, 3H), 1.55-1.63 (m, 4H).

後処理

  1. customTo a 20 mL vial equipped with a magnetic stirring bar
  2. washThe organic extracts were washed with saturated aq. NaCl (5×10 mL), 1% aq NaOH (1×10 mL), and 0.1 N HCl (1×10 mL)
  3. dry with materialThe organic extracts were dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customto afford a yellow oil, which
  6. customwas purified by preparative HPLC

出典と根拠

ORDレコード
ord-56dcdd05995a4b0c86d76672d40ede54
出典データセット
uspto-grants-2009_08
特許番号
US07576106B2

反応ノート

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