Diisopropylethylamine → 5-(12-fluoro-7-oxo-6,7-dihydro-5H-pyrido[2',3':3,4]azepino[1,2-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595746Notes

Reaction equation

HRID 595746 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]1[C:16]([CH2:17][CH2:18][C:19]([OH:21])=O)=[CH:15][CH:14]=[C:13]([C:22]3[C:23]([N:42]([CH3:47])[S:43]([CH3:46])(=[O:45])=[O:44])=[CH:24][C:25]4[O:29][C:28]([C:30]5[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=5)=[C:27]([C:37](=[O:40])[NH:38][CH3:39])[C:26]=4[CH:41]=3)[N:12]=1)[NH:6]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:11]4[N:12]=[C:13]([C:22]5[C:23]([N:42]([CH3:47])[S:43]([CH3:46])(=[O:44])=[O:45])=[CH:24][C:25]6[O:29][C:28]([C:30]7[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=7)=[C:27]([C:37]([NH:38][CH3:39])=[O:40])[C:26]=6[CH:41]=5)[CH:14]=[CH:15][C:16]=4[CH2:17][CH2:18][C:19](=[O:21])[N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 903334323-(2-(4-fluoro-1H-indol-2-yl)-6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)pyridin-3-yl)propanoic acid

Product 1

HCID 903410215-(12-fluoro-7-oxo-6,7-dihydro-5H-pyrido[2',3':3,4]azepino[1,2-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 3-(2-(4-fluoro-1H-indol-2-yl)-6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)pyridin-3-yl)propanoic acid (88 mg, 0.133 mmol) and HATU (126 mg, 0.333 mmol) in DMF (6650 μl) was added DIEA (116 μl, 0.665 mmol). The resultant mixture was stirred for 1 h at ambient temperature then was diluted with EtOAc and washed successively with H2O (3×) and brine (1×). The organic layer was dried over MgSO4, filtered, concentrated in vacuo, and the residue purified by silica gel column chromatography using a gradient of 0-30% EtOAc/CH2Cl2 as eluent. 1H NMR δ (ppm) (CHCl3-d): 8.38 (1H, d, J=8.46 Hz), 8.12 (1H, s), 8.02 (2H, dd, J=8.55, 5.32 Hz), 7.69 (3H, d, J=9.74 Hz), 7.60 (1H, d, J=7.80 Hz), 7.36 (1H, td, J=8.24, 5.56 Hz), 7.25 (2H, t, J=8.60 Hz), 7.02 (1H, t, J=8.68 Hz), 5.95 (1H, br s), 3.35 (3H, s), 3.27˜3.22 (2H, m), 3.20˜3.15 (2H, m), 3.05 (3H, d, J=4.90 Hz), 2.85 (3H, s). MS (M+H)+: 641.

Workup

  1. washwashed successively with H2O (3×) and brine (1×)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customthe residue purified by silica gel column chromatography

Sources & evidence

ORD record
ord-383268cbc4154922b66378f395af7442
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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