Aniline → tert-butyl 6-(2-anilino-2-oxoethyl)-9,10-dichloro-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

HRID 1356307ノート

反応式

HRID 1356307 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)N=C=NC(C)C.[C:17]([O:21][C:22]([N:24]1[CH2:37][CH2:36][C:35]2[C:34]3[C:33]([Cl:38])=[C:32]([Cl:39])[CH:31]=[CH:30][C:29]=3[N:28]([CH2:40][C:41](O)=[O:42])[C:27]=2[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18]>CN(C1C=CN=CC=1)C.C1COCC1.CCOC(C)=O>[NH:1]([C:41](=[O:42])[CH2:40][N:28]1[C:29]2[CH:30]=[CH:31][C:32]([Cl:39])=[C:33]([Cl:38])[C:34]=2[C:35]2[CH2:36][CH2:37][N:24]([C:22]([O:21][C:17]([CH3:19])([CH3:18])[CH3:20])=[O:23])[CH2:25][CH2:26][C:27]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

7

反応物 3

HCID 6115AnilineHCID 12734DiisopropylcarbodiimideHCID 22396560[3-(tert-Butoxycarbonyl)-9,10-dichloro-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl]acetic acid

生成物 1

HCID 22396637tert-butyl 6-(2-anilino-2-oxoethyl)-9,10-dichloro-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate収率 68.2%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

DMAP (60 mg, 0.49 mmol), aniline (0.050 mL, 0.55 mmol) and DIC (0.084 mL, 0.54 mmol) were added to the solution of crude [3-(tert-butoxycarbonyl)-9,10-dichloro-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl]acetic acid (0.20 g, 0.48 mmol) in dry THF (2.5 mL). After 24 h, the reaction was diluted with EtOAc followed by washing with 10% aqueous citric acid (20 mL), saturated aqueous NaHCO3 (20 mL), and brine (20 mL). The organic layer was then dried over Na2SO4, decanted, and concentrated. The crude product was first purified by column chromatography (Biotage, 40S, SIM) with CH2Cl2/EtOAc and yielded 0.16 g of impure product. Then, crystallization from EtOAc/heptane gave 90 mg (37%) of a white solid; mp 208.5-210.0° C.; 1H NMR (300 MHz, DMSO) δ 10.45 (s, 1H), 7.58 (d, J=8.3 Hz, 2H), 7.45 (d, J=9.0 Hz, 1H), 7.30 (m, 3H), 7.07 (m, 1H), 5.08 (br s, 2H), 3.63 (m, 4H), 3.40 (m, 2H), 2.99 (m, 2H), 1.40 (app d, 9H); IR (diffuse reflectance) 3275, 1693, 1671, 1602, 1554, 1449, 1409, 1365, 1319, 1312, 1302, 1254, 1166, 1113, 762 cm−1; MS (EI) m/z 487 (M+), 346, 345, 105, 94, 92, 76, 65, 62, 56, 52; MS (FAB) m/z 488 (M+H+), 488, 487, 434, 433, 432, 431, 388, 57, 42, 41; HRMS (EI) calcd for C25H27Cl2N3O3 487.1429, found 487.1441; Anal. Calcd for C25H27Cl2N3O3: C, 61.48; H, 5.57; N, 8.60; found: C, 61.41; H, 5.70; N, 8.48.

後処理

  1. washby washing with 10% aqueous citric acid (20 mL), saturated aqueous NaHCO3 (20 mL), and brine (20 mL)
  2. dry with materialThe organic layer was then dried over Na2SO4
  3. customdecanted
  4. concentrationconcentrated
  5. customThe crude product was first purified by column chromatography (Biotage, 40S, SIM) with CH2Cl2/EtOAc

出典と根拠

ORDレコード
ord-a021042e00624294b84c858ae61665c7
出典データセット
uspto-grants-2003_07
特許番号
US06586421B2

反応ノート

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