Water → HCID 44538106、化合物

HRID 63425

反応式

HRID 63425 の反応式
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=O)=[CH:5][CH:4]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[NH2:28][CH2:29][C:30]1[CH:31]=[C:32]2[C:36](=[CH:37][CH:38]=1)[C:35](=[O:39])[N:34]([CH:40]1[CH2:45][CH2:44][C:43](=[O:46])[NH:42][C:41]1=[O:47])[CH2:33]2.O>CN(C=O)C>[O:47]=[C:41]1[CH:40]([N:34]2[CH2:33][C:32]3[C:36](=[CH:37][CH:38]=[C:30]([CH2:29][NH:28][C:10](=[O:12])[CH2:9][C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:14])[F:13])=[CH:8][CH:7]=4)[CH:31]=3)[C:35]2=[O:39])[CH2:45][CH2:44][C:43](=[O:46])[NH:42]1

参加物

6

反応物 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 118342(alpha,alpha,alpha-Trifluoro-4-tolyl)acetic acidHCID 665895253-(5-(aminomethyl)-1-oxo-2,3-dihydro-1H-isoindol-2-yl)piperidine-2,6-dione hydrochloride

生成物 1

HCID 44538106HCID 44538106、化合物収率 29.9%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of (α,α,α-trifluoro-p-tolyl) acetic acid (0.33 g, 1.6 mmol) and CDI (0.27 g, 1.7 mmol) was stirred in DMF (20 ml) at 40° C. under N2 for 2 hours. After 2 hours, 3-(5-(aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride (0.50 g, 1.6 mmol) was added. After 2 h, TEA (0.16 g, 1.6 mmol) was added to the mixture and stirring continued for 16 h at this temperature. Water (40 mL) was added, resulting in precipitation of the product. The solids were filtered, washed with water (50 mL) and dried in vacuo providing N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-2-(4-trifluoromethyl-phenyl)-acetamide as an off-white solid (0.22 g, 29% yield); mp 217-219° C.; HPLC, Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 ml/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 3.95 (96.06%); 1H NMR (DMSO-d6) δ 1.98-2.02 (m, 1H), 2.32-2.46 (m, 1H), 2.57-2.63 (m, 1H), 2.86-2.98 (m, 1H), 3.63 (s, 2H), 4.25 (d, 1H, J=17.4), 4.31-4.45 (m, 3H), 5.11 (dd, 1H, J=13.2, J=5.1), 7.37-7.43 (m, 2H), 7.51 (d, 2H, J=7.8), 7.67-7.70 (m, 3H), 8.74 (t, 1H, J=5.7), 10.99 (s, 1H); 13C NMR (DMSO-d6) δ 22.5, 31.2, 41.9, 42.3, 47.0, 51.6, 122.0, 122.9, 124.4 (q, J=269.3), 125.0 (q, J=3.75), 127.1, 127.2 (q, J=31.5), 129.9, 130.4, 141.1, 142.3, 143.6, 167.9, 169.5, 171.0, 172.9; LCMS: MH=460; Anal. Calcd for C23H20F3N3O4+0.5 CH2Cl2: C, 56.24; H, 4.22; N, 8.37. Found: C, 56.10; H, 3.92; N, 8.50.

後処理

  1. waitAfter 2 h
  2. waitcontinued for 16 h at this temperature
  3. customresulting in precipitation of the product
  4. filtrationThe solids were filtered
  5. washwashed with water (50 mL)
  6. customdried in vacuo

出典と根拠

ORDレコード
ord-a46fe05237d548e4a15fa7e4077fd8f7
出典データセット
uspto-grants-2016_09
特許番号
US09447070B2

関連ノート

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