Indoline → HCID 178523688, compound

HRID 1023270Notes

Reaction equation

HRID 1023270 reaction equation
Cl.Cl.Cl.[O:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[C:12]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH2:27])[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[C:7]=2[O:6][CH2:5]1.C(N(CC)C(C)C)(C)C.ClC(Cl)(O[C:41](=[O:47])OC(Cl)(Cl)Cl)Cl.[NH:49]1[C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH2:51][CH2:50]1>C(Cl)Cl>[O:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[C:12]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH:27][C:41]([N:49]5[C:57]6[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=6)[CH2:51][CH2:50]5)=[O:47])[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[C:7]=2[O:6][CH2:5]1

Participants

6

Reactant 4

HCID 10328IndolineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 178478587HCID 178478587, compound2×

Product 1

HCID 178523688HCID 178523688, compoundYield 68.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of N-trans-4-[2-(4-Benzo[1,3]dioxol-4-yl-piperazin-1-yl)-ethyl]-cyclohexylamine hydrochloride (Intermediate A) (31.1 mg, 85 μmol) in DCM (1 ml) at room temperature N,N-diisopropylethylamine (110 mg, 148 μl, 850 μmol, Eq: 10) and triphosgene (27.7 mg, 93.5 μmol, Eq: 1.1) was added carefully and the solution stirred for minutes at room temperature. Indoline (12.2 mg, 102 μmol, Eq: 1.2) was added and stirred for 30 minutes at room temperature. The reaction mixture was quenched with 10 mL sat NaHCO3 and extracted with DCM (3×15 mL). The organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 100 g, 0% to 10% MeOH in DCM) to yield the title compound as an white solid (27.6 mg, 68.1%), MS (ISP) m/z=477.2 [(M+H)+].

Workup

  1. additionwas added carefully
  2. stirringstirred for 30 minutes at room temperature
  3. customThe reaction mixture was quenched with 10 mL
  4. extractionextracted with DCM (3×15 mL)
  5. dry with materialThe organic layers were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 100 g, 0% to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-a27be01a6f4646c091b2c1a0391e4a2b
Source dataset
uspto-grants-2014_05
Patent number
US08722683B2

Reaction notes

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