Diisopropylethylamine → Methyl 6-[{[3-({3-[(4-{2-[4-(methoxycarbonyl)phenyl]ethyl}phenyl)carbamoyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl}carbamoyl)phenyl]sulfonyl}(propyl)amino]nicotinate

HRID 926069Notes

Reaction equation

HRID 926069 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[CH2:31][CH2:30][CH2:29][CH2:28][C:5]=2[C:6]=1[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][C:18]2[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][CH:19]=2)=[CH:12][CH:11]=1)=[O:8].[CH3:32][O:33][C:34]([C:36]1[CH:37]=[CH:38][C:39]([N:42]([CH2:55][CH2:56][CH3:57])[S:43]([C:46]2[CH:47]=[C:48]([CH:52]=[CH:53][CH:54]=2)[C:49](O)=[O:50])(=[O:45])=[O:44])=[N:40][CH:41]=1)=[O:35].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C>O.CN(C=O)C>[CH3:25][O:24][C:22]([C:21]1[CH:20]=[CH:19][C:18]([CH2:17][CH2:16][C:13]2[CH:12]=[CH:11][C:10]([NH:9][C:7]([C:6]3[C:5]4[CH2:28][CH2:29][CH2:30][CH2:31][C:4]=4[S:3][C:2]=3[NH:1][C:49]([C:48]3[CH:47]=[C:46]([S:43]([N:42]([CH2:55][CH2:56][CH3:57])[C:39]4[CH:38]=[CH:37][C:36]([C:34]([O:33][CH3:32])=[O:35])=[CH:41][N:40]=4)(=[O:45])=[O:44])[CH:54]=[CH:53][CH:52]=3)=[O:50])=[O:8])=[CH:15][CH:14]=2)=[CH:27][CH:26]=1)=[O:23]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68207883Methyl 4-[2-(4-{[(2-amino-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}phenyl)ethyl]benzoateHCID 712387833-{[5-(Methoxycarbonyl)pyridin-2-yl](propyl)sulfamoyl}benzoic acid

Product 1

HCID 71238544Methyl 6-[{[3-({3-[(4-{2-[4-(methoxycarbonyl)phenyl]ethyl}phenyl)carbamoyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl}carbamoyl)phenyl]sulfonyl}(propyl)amino]nicotinateYield 60.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 100 mg of methyl 4-[2-(4-{[(2-amino-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}phenyl)ethyl]benzoate and 2 mL of DMF were added 105 mg of 3-{[5-(methoxycarbonyl)pyridin-2-yl](propyl)sulfamoyl}benzoic acid, 110 mg of HATU, and 0.060 mL of N-ethyl diisopropylamine, followed by stirring at room temperature for 5 hours. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 110 mg of methyl 6-[{[3-({3-[(4-{2-[4-(methoxycarbonyl)phenyl]ethyl}phenyl)carbamoyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl}carbamoyl)phenyl]sulfonyl}(propyl)amino]nicotinate as a pale brown powder.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-84b22f9fe13049c3a679209e4c686d18
Source dataset
uspto-grants-2016_03
Patent number
US09284295B2

Reaction notes

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