Acetic Acid → ethyl 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)amino)acetate

HRID 1776865Notes

Reaction equation

HRID 1776865 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.O=[CH:48][C:49]([O:51][CH2:52][CH3:53])=[O:50].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>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][CH2:48][C:49]([O:51][CH2:52][CH3:53])=[O:50])[N:8]3[C:9]=2[CH:10]=[CH:11][CH:12]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 70211Ethyl oxoacetateHCID 5049666Sodium triacetoxyborohydrideHCID 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 86728268ethyl 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)amino)acetateYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution 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 (200 mg, 0.31 mmol) and ethyl 2-oxoacetate (64 mg, 0.62 mmol) in CH2Cl2 (4 mL) was added acetic acid (4 mg, 0.06 mmol). The mixture was stirred at room temperature for 1 hour, and then NaBH(AcO)3 (144 mg, 0.68 mmol) added to the mixture. After stirring overnight, the mixture diluted with CH2Cl2, washed with brine, dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using prep-HPLC give the product of ethyl 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)amino)acetate (45 mg, yield: 20%). 1H-NMR (CDCl3, 400 MHz) δ 8.01 (s, 1H), 7.96 (dd, J=8.4, 5.2 Hz, 2H), 7.67 (s, 1H), 7.50 (s, 2H), 7.13˜7.25 (m, 5H), 6.84 (dd, J=9.2, 8.0 Hz, 1H), 6.50 (dd, J=7.6, 3.6 Hz, 1H), 5.99 (br s, 1H), 4.12 (q, J=7.2 Hz, 2H), 3.29˜3.44 (m, 5H), 3.20 (dd, J=12.8, 8.4 Hz, 1H), 3.00 (d, J=4.8 Hz, 3H), 2.86˜2.96 (m, 1H), 2.67 (s, 3H), 1.22 (t, J=7.2 Hz, 3H). MS (M+H)+: 730.

Workup

  1. stirringAfter stirring overnight
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified

Sources & evidence

ORD record
ord-43b94a961f0b40069513223b76e62b2f
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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