Triethylamine → HCID 86728260, compound

HRID 1776857Notes

Reaction equation

HRID 1776857 reaction equation
[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:14]4[N:15]=[C:16]([C:19]5[C:20]([N:39]([CH3:44])[S:40]([CH3:43])(=[O:42])=[O:41])=[CH:21][C:22]6[O:26][C:25]([C:27]7[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=7)=[C:24]([C:34]([NH:36][CH3:37])=[O:35])[C:23]=6[CH:38]=5)[CH:17]=[CH:18][C:13]=4[O:12][CH:11]([CH2:45][OH:46])[N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1.[C:47]([NH:54][C@H:55]([C:59](O)=[O:60])[CH:56]([CH3:58])[CH3:57])([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48].CCN=C=NCCCN(C)C.CCN(CC)CC>ClCCl.CN(C1C=CN=CC=1)C.O>[C:50]([O:49][C:47]([NH:54][C@@H:55]([CH:56]([CH3:58])[CH3:57])[C:59]([O:46][CH2:45][CH:11]1[N:6]2[C:7]3[CH:8]=[CH:9][CH:10]=[C:2]([F:1])[C:3]=3[CH:4]=[C:5]2[C:14]2[N:15]=[C:16]([C:19]3[C:20]([N:39]([CH3:44])[S:40]([CH3:43])(=[O:42])=[O:41])=[CH:21][C:22]4[O:26][C:25]([C:27]5[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=5)=[C:24]([C:34](=[O:35])[NH:36][CH3:37])[C:23]=4[CH:38]=3)[CH:17]=[CH:18][C:13]=2[O:12]1)=[O:60])=[O:48])([CH3:53])([CH3:52])[CH3:51]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 83693Boc-L-ValineHCID 86728261HCID 86728261, compound2×

Product 1

HCID 86728260HCID 86728260, compoundYield 76%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(11-fluoro-6-(hydroxymethyl)-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 (30 mg, 0.05 mmol, Compound 87, single enantiomer) and N-Boc-L-Valine (20 mg, 0.09 mmol) in dichloromethane, EDCI (20 mg, 0.10 mmol), DMAP (8 mg, 0.06 mmol) and Et3N (0.01 mL) were added. The reaction mixture was stirred at room temperature overnight. Then H2O was added, and extracted with dichloromethane. The combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified using prep-TLC (dichloromethane:MeOH=40:1) to provide (2S)-(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 2-((tert-butoxycarbonyl)amino)-3-methylbutanoate (30 mg, yield: 76%). 1H-NMR (CDCl3, 400 MHz) δ 7.98˜8.02 (m, 3H), 7.67 (s, 1H), 7.46˜7.54 (m, 2H), 7.19˜7.25 (m, 5H), 6.84˜6.89 (m, 1H), 6.62˜6.65 (m, 1H), 5.98 (br s, 1H), 4.91 (d, J=8.4 Hz, 1H), 4.42˜4.48 (m, 1H), 4.30˜4.35 (m, 1H), 4.18 (br s, 1H), 3.38 (s, 3H), 3.01 (d, J=4.8 Hz, 3H), 2.72 (s, 3H), 1.90˜1.95 (m, 1H), 1.45 (s, 9H), 0.88 (d, J=6.4 Hz, 3H), 0.79 (d, J=6.4 Hz, 3H). MS (M+H)+: 844.

Workup

  1. extractionextracted with dichloromethane
  2. washThe combined organic phases were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified

Sources & evidence

ORD record
ord-fdbdef23dfe740b9802da4c9bbfab92e
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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