Triethylamine → (2S)-methyl 2-(((11-fluoro-2-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-6-yl)methyl)carbamoyl)pyrrolidine-1-carboxylate

HRID 1776870Notes

Reaction equation

HRID 1776870 reaction equation
[NH2:1][CH2:2][CH:3]1[N:8]2[C:9]3[CH:10]=[CH:11][CH:12]=[C:13]([F:16])[C:14]=3[CH:15]=[C:7]2[C:6]2[N:17]=[C:18]([C:21]3[C:22]([N:41]([CH3:46])[S:42]([CH3:45])(=[O:44])=[O:43])=[CH:23][C:24]4[O:28][C:27]([C:29]5[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=5)=[C:26]([C:36]([NH:38][CH3:39])=[O:37])[C:25]=4[CH:40]=3)[CH:19]=[CH:20][C:5]=2[O:4]1.[CH3:47][O:48][C:49]([N:51]1[CH2:55][CH2:54][CH2:53][C@H:52]1[C:56](O)=[O:57])=[O:50].CCN=C=NCCCN(C)C.C(N(CC)CC)C>CN(C1C=CN=CC=1)C.C(Cl)Cl>[F:16][C:13]1[C:14]2[CH:15]=[C:7]3[C:6]4[N:17]=[C:18]([C:21]5[C:22]([N:41]([CH3:46])[S:42]([CH3:45])(=[O:43])=[O:44])=[CH:23][C:24]6[O:28][C:27]([C:29]7[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=7)=[C:26]([C:36](=[O:37])[NH:38][CH3:39])[C:25]=6[CH:40]=5)[CH:19]=[CH:20][C:5]=4[O:4][CH:3]([CH2:2][NH:1][C:56]([C@@H:52]4[CH2:53][CH2:54][CH2:55][N:51]4[C:49]([O:48][CH3:47])=[O:50])=[O:57])[N:8]3[C:9]=2[CH:10]=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 11095105N-Carbomethoxy prolineHCID 867282695-(6-(aminomethyl)-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Product 1

HCID 86728273(2S)-methyl 2-(((11-fluoro-2-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-6-yl)methyl)carbamoyl)pyrrolidine-1-carboxylateYield 69%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-(6-(aminomethyl)-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (70 mg, 0.11 mmol), (S)-1-(methoxycarbonyl)pyrrolidine-2-carboxylic acid (38 mg, 0.22 mmol), EDCI (12 mg, 0.27 mmol), DMAP (40 mg, 0.33 mmol) and triethylamine (33 mg, 0.33 mmol) in CH2Cl2 (2 mL) was stirred at room temperature overnight. The mixture was then purified using Prep-TLC(CH2Cl2:EtOAc=1:1) to provide (2S)-methyl 2-(((11-fluoro-2-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-6-yl)methyl)carbamoyl)pyrrolidine-1-carboxylate (60 mg, yield: 69.0%). 1H-NMR (CDCl3, 400 MHz) δ 7.86˜8.05 (m, 3H), 7.28˜7.69 (m, 4H), 7.16˜7.27 (m, 5H), 6.85 (d, J=9.2 Hz, 1H), 6.60 (dd, J=5.2, 7.2 Hz, 1H), 5.98˜6.25 (m, 1H), 4.31 (br. s, 1H), 3.65 (br. s, 5H), 3.39 (s, 5H), 2.97 (d, J=3.2 Hz, 3H), 2.72 (br. s, 3H), 1.90˜2.49 (m, 2H), 1.63˜1.79 (m, 2H). MS (M+H)+: 799.

Workup

  1. customThe mixture was then purified

Sources & evidence

ORD record
ord-a1c05a645b8a4e96878ba13eccc47e8a
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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