1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 74931390, compound

HRID 1095088Notes

Reaction equation

HRID 1095088 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:42])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24]3[CH:29]=[C:28]([I:30])[CH:27]=[CH:26][C:25]=3[O:31][CH:32]3[CH2:37][CH2:36][N:35]([CH2:38][C:39](O)=[O:40])[CH2:34][CH2:33]3)[C:5]2=[CH:4][CH:3]=1.CC[N:45]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.[NH4+].[Cl-]>CN(C)C=O>[C:39]([CH2:38][N:35]1[CH2:36][CH2:37][CH:32]([O:31][C:25]2[CH:26]=[CH:27][C:28]([I:30])=[CH:29][C:24]=2[CH:11]2[C:10]3([C:5]4[C:6](=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)[NH:8][C:9]3=[O:42])[CH:15]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=3)[CH2:14][C:13](=[O:23])[NH:12]2)[CH2:33][CH2:34]1)(=[O:40])[NH2:45]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 86631792HCID 86631792, compound

Product 1

HCID 74931390HCID 74931390, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of racemic(2′R, 3R, 4′S)-6-chloro-4′-(3-chlorophenyl)-2′-[2-(1-hydroxycarbonylmethyl-4-piperidinyloxy)-5-iodo-phenyl]spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (50 mg, 0.069 mmol) in anhydrous N,N-dimethylformamide (2 mL) was added EDCI (26.5 mg, 0.139 mmol), HOBT (18.8 mg, 0.139 mmol), diisopropylethylamine (35.9 mg, 0.278 mmol), NH4Cl (7.4 mg, 0.278 mmol). The reaction mixture was heated at 80° C. for 1 h, then cooled to room temperature. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (MeOH:EtOAc=8:92) to give racemic(2′R, 3R, 4′S)-2′-[2-(1-carbamoylmethyl-4-piperidinyloxy)-5-iodo-phenyl]-6-chloro-4′-(3-chlorophenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as an off white solid (Yield 25.6 mg, 51%)

Workup

  1. temperaturecooled to room temperature
  2. customThe mixture was partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography (MeOH:EtOAc=8:92)

Sources & evidence

ORD record
ord-021b290694cc456d8777abad8e1ad236
Source dataset
uspto-grants-2012_03
Patent number
US08134001B2

Reaction notes

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