P-Anisidine → tert-Butyl 9,10-dichloro-6-[2-(4-methoxyanilino)-2-oxoethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

HRID 1356309ノート

反応式

HRID 1356309 の反応式
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][CH:4]=1.CC(C)N=C=NC(C)C.[C:19]([O:23][C:24]([N:26]1[CH2:39][CH2:38][C:37]2[C:36]3[C:35]([Cl:40])=[C:34]([Cl:41])[CH:33]=[CH:32][C:31]=3[N:30]([CH2:42][C:43](O)=[O:44])[C:29]=2[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20]>CN(C1C=CN=CC=1)C.C1COCC1.CCOC(C)=O>[Cl:41][C:34]1[CH:33]=[CH:32][C:31]2[N:30]([CH2:42][C:43]([NH:9][C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)=[O:44])[C:29]3[CH2:28][CH2:27][N:26]([C:24]([O:23][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:25])[CH2:39][CH2:38][C:37]=3[C:36]=2[C:35]=1[Cl:40]

参加物

7

反応物 3

HCID 7732P-Anisidine2 回HCID 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 22396814tert-Butyl 9,10-dichloro-6-[2-(4-methoxyanilino)-2-oxoethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate収率 37%

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 (89 mg, 0.73 mmol), p-anisidine (0.10 g, 0.81 mmol) and DIC (0.13 mL, 0.81 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 (0.30 g, 0.73 mmol) in dry THF (3.5 mL). After 4 h, additional p-anisidine (45 mg, 0.37 mmol) was added. The reaction was diluted with EtOAc after another 17 h and washed 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 impure product. It was then crystallized from EtOAc/heptane, triturated with pentane, and recrystallized from EtOAc/heptane to give 0.14 g (36%) of a white solid: mp 143.0-144.0° C.; 1H NMR (300 MHz, DMSO) δ 10.30 (s, 1H), 7.47 (m, 3H), 7.25 (d, J=8.7 Hz, 1H), 6.88 (d, J=9.0 Hz, 2H), 5.04 (br s, 2H), 3.71 (s, 3H), 3.63 (m, 4H), 3.39 (m, 2H), 2.99 (m, 2H), 1.40 (app d, 9H); IR (diffuse reflectance) 2975, 1666, 1545, 1514, 1474, 1451, 1414, 1365, 1253, 1239, 1222, 1173, 1158, 830, 784 cm−1; MS (EI) m/z 517 (M+), 377, 375, 227, 224, 212, 134, 124, 121, 55, 53; MS (FAB) m/z 518 (M+H+), 520, 519, 518, 517, 464, 463, 462, 461, 418, 57; HRMS (EI) calcd for C26H29Cl2N3O4 517.1535, found 517.1537; Anal. Calcd for C26H29Cl2N3O4; C, 60.24; H, 5.64; N, 8.10; found: C, 59.86; H, 5.68; N, 7.94.

後処理

  1. washwashed 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 impure product
  5. customIt was then crystallized from EtOAc/heptane
  6. customtriturated with pentane
  7. customrecrystallized from EtOAc/heptane

出典と根拠

ORDレコード
ord-80874b4769994e76af201c94fc16874b
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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