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

HRID 2306995Notes

Reaction equation

HRID 2306995 reaction equation
[CH3:1][C:2]1[C:8]([CH3:9])=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].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:4][C:3]3[CH:5]=[CH:6][CH:7]=[C:8]([CH3:9])[C:2]=3[CH3:1])=[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]

Participants

7

Reactant 3

HCID 68932,3-Dimethylaniline2×HCID 12734DiisopropylcarbodiimideHCID 22396560[3-(tert-Butoxycarbonyl)-9,10-dichloro-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl]acetic acid

Product 1

HCID 22396642tert-Butyl 9,10-dichloro-6-[2-(2,3-dimethylanilino)-2-oxoethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylateYield 58.4%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

DMAP (89 mg, 0.73 mmol), 2,3-dimethylaniline (98 mg, 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 2,3-dimethylaniline (0.049 mL, 0.40 mmol) and THF (2 mL) was added. The reaction was diluted with EtOAc after 25 h followed by washing with 10% aqueous citric acid (75 mL), saturated aqueous NaHCO3 (40 mL), and brine (40 mL). A precipitate in the combined organic layers was filtered to yield 0.22 g (58%) white solid: mp 232.5-233.0° C.; 1H NMR (DMSO, 400 MHz) δ 9.77 (s, 1H), 7.49 (d, J=8.8 Hz, 1H), 7.28 (d, J=8.7 Hz, 1H), 7.13 (d, J=6.8 Hz, 1H), 7.03 (m, 2H), 5.11 (s, 2H), 3.64 (m, 4H), 3.39 (m, 2H), 3.03 (m, 2H), 2.24 (s, 3H), 2.09 (s, 3H), 1.41 (s, 9H); IR (diffuse reflectance) 2977, 1692, 1659, 1541, 1474, 1451, 1412, 1366, 1303, 1269, 1201, 1174, 1112, 791, 773 cm−1; MS (EI) m/z 515 (M+), 376, 226, 224, 212, 189, 149, 133, 119, 55, 52; HRMS (EI) calcd for C27H31Cl2N3O3 515.1743, found 515.1747.

Workup

  1. washby washing with 10% aqueous citric acid (75 mL), saturated aqueous NaHCO3 (40 mL), and brine (40 mL)
  2. filtrationA precipitate in the combined organic layers was filtered

Sources & evidence

ORD record
ord-68feb5e51e134b138186ae28f841fdde
Source dataset
uspto-grants-2004_12
Patent number
US06828314B2

Reaction notes

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