Tetrahydrofuran → methyl 3-cyclohexyl-1-methyl-2-{2-[2-(methyl {2-[2-(methylamino)ethoxy]ethyl}amino)-2-oxoethoxy]phenyl}-1H-indole-6-carboxylate

HRID 1807633Notes

Reaction equation

HRID 1807633 reaction equation
[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=3)[N:9]([CH3:20])[C:8]=2[C:21]2[CH:31]=[CH:30][CH:29]=CC=2OCC(O)=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:32][NH:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][NH:39][CH3:40].C(N(C(C)C)CC)(C)C.CN(C([O:57]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:74]1[CH2:78][O:77][CH2:76][CH2:75]1>>[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=3)[N:9]([CH3:20])[C:8]=2[C:21]2[CH:31]=[CH:30][CH:29]=[CH:75][C:76]=2[O:77][CH2:78][C:74]([N:33]([CH3:32])[CH2:34][CH2:35][O:36][CH2:37][CH2:38][NH:39][CH3:40])=[O:57])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 27247701,5-Bis(methylamino)-3-oxapentaneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58317804{2-[3-cyclohexyl-6-(methoxycarbonyl)-1-methyl-1H-indol-2-yl]phenoxy}acetic acid

Product 1

HCID 67226641methyl 3-cyclohexyl-1-methyl-2-{2-[2-(methyl {2-[2-(methylamino)ethoxy]ethyl}amino)-2-oxoethoxy]phenyl}-1H-indole-6-carboxylateYield 91%

Procedure

A solution of intermediate 5 (650 mg, 1.54 mmol), N-methyl-2-(methylaminoethyloxy)ethylamine (1.02 g, 7.71 mmol), diisopropylethylamine (808 μL, 4.63 mmol) and HATU (880 mg, 2.31 mmol) in dry THF (25 mL) was stirred at room temperature overnight. Then, the reaction mixture was concentrated under vacuum. The residue was partitioned between AcOEt and water. The organic layer was dried over anhydrous Na2SO4 and evaporated to yield 750 mg (91%) of methyl 3-cyclohexyl-1-methyl-2-{2-[2-(methyl {2-[2-(methylamino)ethoxy]ethyl}amino)-2-oxoethoxy]phenyl}-1H-indole-6-carboxylate 6: m/z=536 (M+H)+.

Workup

  1. concentrationThen, the reaction mixture was concentrated under vacuum
  2. customThe residue was partitioned between AcOEt and water
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. customevaporated

Sources & evidence

ORD record
ord-2c2354355fb646f085656da99cee0b0c
Source dataset
uspto-grants-2013_01
Patent number
US08357687B2

Reaction notes

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