1,2-Dichloroethane → HCID 59375067、化合物

HRID 661935ノート

反応式

HRID 661935 の反応式
[NH2:1][CH2:2][C:3]1[CH:15]=[C:14]2[C:6]([C:7]3[C:8]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([N:25]5[CH2:33][C:32]6[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=6)[C:26]5=[O:34])[C:20]=4[CH3:35])=[CH:9][CH:10]=[C:11]([C:16]([NH2:18])=[O:17])[C:12]=3[NH:13]2)=[CH:5][CH:4]=1.[C:36](O)(=[O:39])[CH2:37][OH:38].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>C(#N)C.C1COCC1>[OH:39][CH2:36][C:37]([NH:1][CH2:2][C:3]1[CH:15]=[C:14]2[C:6]([C:7]3[C:8]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([N:25]5[CH2:33][C:32]6[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=6)[C:26]5=[O:34])[C:20]=4[CH3:35])=[CH:9][CH:10]=[C:11]([C:16]([NH2:18])=[O:17])[C:12]=3[NH:13]2)=[CH:5][CH:4]=1)=[O:38]

参加物

8

反応物 6

HCID 111,2-DichloroethaneHCID 757Glycolic AcidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 59375043HCID 59375043、化合物

生成物 1

HCID 59375067HCID 59375067、化合物収率 60.7%

試薬・触媒・溶媒 1

HCID 22177404Acetonitrile tetrahydrofuran溶媒

実験手順

A solution of crude 7-(aminomethyl)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 33-1, 25 mg, 0.054 mmol), glycolic acid (8.26 mg, 0.109 mmol), HOAT (13.30 mg, 0.098 mmol), and EDC (20.81 mg, 0.109 mmol) in acetonitrile-THF (2:1) (5 mL) was treated with DIEA (0.028 mL, 0.163 mmol) and stirred at rt overnight. The mixture was concentrated and purified by preparative HPLC. The appropriate effluent fractions were concentrated to afford an aqueous suspension, which was treated with NaHCO3 (aq). The precipitate was collected by filtration, washed with water and dried to provide 7-((2-hydroxyacetamido)methyl)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (17 mg, 59%). 1H NMR (400 MHz, DMSO-d6) δ 11.49 (1H, s), 8.22-8.28 (1H, m), 8.17 (1H, br. s.), 7.97-8.05 (1H, m), 7.81 (1H, d, J=7.5 Hz), 7.69 (2H, d, J=3.7 Hz), 7.54-7.66 (3H, m), 7.42-7.54 (2H, m), 7.28-7.38 (1H, m), 7.03 (1H, d, J=7.9 Hz), 6.94-7.00 (1H, m), 6.86-6.94 (1H, m), 5.45 (1H, br.), 4.88-5.05 (2H, m), 4.33-4.48 (2H, m), 3.88 (2H, s), 1.83 (3H, s). Mass spectrum m/z 519.2 (M+H)+.

後処理

  1. concentrationThe mixture was concentrated
  2. custompurified by preparative HPLC
  3. concentrationThe appropriate effluent fractions were concentrated
  4. customto afford an aqueous suspension, which
  5. filtrationThe precipitate was collected by filtration
  6. washwashed with water
  7. customdried

出典と根拠

ORDレコード
ord-81e73f05c7664320ada7ff3e027732e4
出典データセット
uspto-grants-2011_12
特許番号
US08084620B2

反応ノート

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