Hydrochloric Acid → N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-3-trifluoromethyl-benzamide

HRID 63414

反応式

HRID 63414 の反応式
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[CH2:7]2.[F:22][C:23]([F:34])([F:33])[C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27](Cl)=[O:28].C(N(CC)CC)C.Cl>CN(C)C=O>[O:21]=[C:15]1[CH:14]([N:8]2[CH2:7][C:6]3[C:10](=[CH:11][CH:12]=[C:4]([CH2:3][NH:2][C:27](=[O:28])[C:26]4[CH:30]=[CH:31][CH:32]=[C:24]([C:23]([F:22])([F:33])[F:34])[CH:25]=4)[CH:5]=3)[C:9]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 752573-(Trifluoromethyl)benzoyl chlorideHCID 665895253-(5-(aminomethyl)-1-oxo-2,3-dihydro-1H-isoindol-2-yl)piperidine-2,6-dione hydrochloride

生成物 1

HCID 44539604N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-3-trifluoromethyl-benzamide収率 66.7%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a stirred mixture of 3-(5-Aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (1.00 g, 3.20 mmol) and 3-(trifluoromethyl)benzoyl chloride (0.67 g, 3.20 mmol) in N,N-dimethylformamide (25 mL), was added triethylamine (0.90 mL, 6.40 mmol) at room temperature under nitrogen. After 1 h, 1N aq. HCl (50 mL) was added and the mixture was stirred for 10 min. The product was isolated by filtration, washed with 1N aq. HCl (50 mL) and water (50 mL). The solids were dissolved in EtOAc (75 mL) and washed with water (75 mL). The organic layer was separated, dried (MgSO4) and concentrated in vacuo to give N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-3-trifluoromethyl-benzamide as an off-white solid (0.95 g, 66% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 3.69 min (98.71%); mp: 244-246° C.; 1H NMR (DMSO-d6) δ 1.94-2.06 (m, 1H), 2.27-2.46 (m, 1H), 2.53-2.68 (m, 1H), 2.80-3.04 (m, 1H), 4.32 (d, J=17.4 Hz, 1H), 4.45 (d, J=17.4 Hz, 1H), 4.63 (d, J=5.9 Hz, 2H), 5.11 (dd, J=5.0, 13.3 Hz, 1H), 7.49 (d, J=7.7 Hz, 1H), 7.57 (s, 1H), 7.66-7.82 (m, 2H), 7.94 (d, J=7.7 Hz, 1H), 8.16-8.34 (m, 2H), 9.42 (t, J=5.8 Hz, 1H), 10.98 (s, 1H); 13C NMR (DMSO-d6) δ 22.50, 31.19, 42.90, 47.14, 51.59, 122.21, 122.99, 123.86 (q, J=3.6 Hz), 123.90 (q, J=270 Hz), 127.18, 127.94 (q, J=3.5 Hz), 129.2 (q, J=32 Hz), 129.71, 130.47, 131.44, 134.97, 142.42, 143.50, 164.79, 167.91, 170.98, 172.85. LCMS: MH=446; Anal Calcd for C22H18N3O4F3+0.6H2O: C, 57.92; H, 4.24; N, 9.21. Found: C, 57.87; H, 4.08; N, 9.16.

後処理

  1. customThe product was isolated by filtration
  2. washwashed with 1N aq. HCl (50 mL) and water (50 mL)
  3. dissolutionThe solids were dissolved in EtOAc (75 mL)
  4. washwashed with water (75 mL)
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-8827a2dce38f410c9f82edaee2a48182
出典データセット
uspto-grants-2016_09
特許番号
US09447070B2

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