Diisopropylethylamine → (1,1-Dioxido-4-thiomorpholinyl)[5-[[1-(1-methylethyl)-4-piperidinyl]oxy]-1-(2,2,2-trifluoroethyl)-1H-indol-2-yl]methanone

HRID 493985Notes

Reaction equation

HRID 493985 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH2:20][C:21]([F:24])([F:23])[F:22])[C:15]([C:25]([OH:27])=O)=[CH:14]3)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[Cl-].[Li+].[NH:30]1[CH2:35][CH2:34][S:33](=[O:37])(=[O:36])[CH2:32][CH2:31]1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[O:36]=[S:33]1(=[O:37])[CH2:34][CH2:35][N:30]([C:25]([C:15]2[N:16]([CH2:20][C:21]([F:22])([F:24])[F:23])[C:17]3[C:13]([CH:14]=2)=[CH:12][C:11]([O:10][CH:7]2[CH2:8][CH2:9][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6]2)=[CH:19][CH:18]=3)=[O:27])[CH2:31][CH2:32]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 433294Lithium ChlorideHCID 6484228Thiomorpholine 1,1-dioxideHCID 67073105HCID 67073105, compound

Product 1

HCID 16112805(1,1-Dioxido-4-thiomorpholinyl)[5-[[1-(1-methylethyl)-4-piperidinyl]oxy]-1-(2,2,2-trifluoroethyl)-1H-indol-2-yl]methanoneYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-(1-isopropyl-piperidin-4-yloxy)-1-(2,2,2-trifluoro-ethyl)-1H-indole-2-carboxylic acid, hydrochloric salt with one equivalent of lithium chloride (650 mg, 1.0 eq.), 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethylurunium tetrafluoroborate (563 mg, 1.2 eq.), thiomorpholine-1,1-dioxide (purchased at Syntec, ref. M1201) and diisopropylethylamine (1.22 mL, 5 eq.) in dimethylformamide was stirred at room temperature for 24 h and then partitioned between an aqueous solution of sodium hydrogenocarbonate and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water and brine, dried over sodium sulfate, filtered, evaporated in vacuo and purified on silica eluting with dichloromethane/methanol/ammoniac. One fraction was isolated and dried in vacuo, to yield 468 mg (66%) of the desired product as off-white solid. MS (m/e): 502.5 (MH+, 100%).

Workup

  1. custompartitioned between an aqueous solution of sodium hydrogenocarbonate and ethyl acetate
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe combined organic layers were washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. custompurified on silica eluting with dichloromethane/methanol/ammoniac
  8. customOne fraction was isolated
  9. customdried in vacuo

Sources & evidence

ORD record
ord-1e45d9c906104cf78d1afcebaebf6953
Source dataset
uspto-grants-2009_05
Patent number
US07538101B2

Reaction notes

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