Indoline → HCID 66626628, compound

HRID 1961626Notes

Reaction equation

HRID 1961626 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][CH:13]([C:16]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)=[O:17])[CH2:12][CH2:11]2)[CH2:4][CH2:3]1.C(N(C(C)C)C(C)C)C.ClC(Cl)(O[C:38](=[O:44])OC(Cl)(Cl)Cl)Cl.[NH:46]1[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH2:48][CH2:47]1>ClCCl>[F:24][C:21]1[CH:22]=[CH:23][C:18]([C:16]([CH:13]2[CH2:12][CH2:11][N:10]([CH2:9][CH2:8][CH:5]3[CH2:6][CH2:7][CH:2]([NH:1][C:38]([N:46]4[C:54]5[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=5)[CH2:48][CH2:47]4)=[O:44])[CH2:3][CH2:4]3)[CH2:15][CH2:14]2)=[O:17])=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 10328IndolineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 178511515HCID 178511515, compound2×

Product 1

HCID 66626628HCID 66626628, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trans {1-[2-(4-amino-cyclohexyl)-ethyl]-piperidin-4-yl}-(4-fluoro-phenyl)-methanone (example 1, intermediate F) (80 mg, 0.24 mmol) was dissolved in 1.5 ml dichloromethane and N-ethyldiisopropylamine (0.33 ml, 1.93 mmol) was added. Triphosgene (79 mg, 0.27 mmol) was added carefully and the solution stirred for 30 minutes at room temperature. Indoline (32 mg, 0.27 mmol) was added and stirred for 30 minutes at room temperature. The reaction mixture was extracted with sat. NaHCO3-solution and dichloromethane. The organic extracts were washed with brine, dried with sodium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel (dichloromethane/methanol 100:0->90:10 gradient). The desired compound was obtained as a white solid (51 mg, 44%), MS: m/e=478.2 (M+H+).

Workup

  1. stirringstirred for 30 minutes at room temperature
  2. extractionThe reaction mixture was extracted with sat. NaHCO3-solution and dichloromethane
  3. washThe organic extracts were washed with brine
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by flash chromatography on silica gel (dichloromethane/methanol 100:0->90:10 gradient)

Sources & evidence

ORD record
ord-c3e909ce1e4b4654a33b5cd9e189c0ce
Source dataset
uspto-grants-2013_04
Patent number
US08415350B2

Reaction notes

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