Dimethylamine → 6-chloro-4'-[5-chloro-2-(2-dimethylcarbamoyl-2-methyl-propoxy)-phenyl]-2'-(5-fluoro-2-methylphenyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 504480Notes

Reaction equation

HRID 504480 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:40])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][CH2:24][C:25]([C:28](O)=[O:29])([CH3:27])[CH3:26])[CH2:14][C:13](=[O:31])[NH:12][CH:11]3[C:32]3[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=3[CH3:39])[C:5]2=[CH:4][CH:3]=1.[CH3:41][NH:42][CH3:43].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:40])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][CH2:24][C:25]([C:28](=[O:29])[N:42]([CH3:43])[CH3:41])([CH3:26])[CH3:27])[CH2:14][C:13](=[O:31])[NH:12][CH:11]3[C:32]3[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=3[CH3:39])[C:5]2=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 674DimethylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 765678616-chloro-4'-[5-chloro-2-(2-hydroxycarbonyl-2-methyl-propoxy)-phenyl]-2'-(5-fluoro-2-methylphenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Product 1

HCID 749287926-chloro-4'-[5-chloro-2-(2-dimethylcarbamoyl-2-methyl-propoxy)-phenyl]-2'-(5-fluoro-2-methylphenyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 23.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of racemic (2′S,3S,4′R)-6-chloro-4′-[5-chloro-2-(2-hydroxycarbonyl-2-methyl-propoxy)-phenyl]-2′-(5-fluoro-2-methylphenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (40 mg, 0.07 mmol), dimethylamine hydrochloric salt (8.2 mg, 0.1 mmol), EDC.HCl (20 mg, 0.1 mmol), and HOBt (14 mg, 0.1 mmol) in THF (5 mL) was added DIPEA (0.018 mL, 0.2 mmol) at r.t. The reaction mixture was stirred for 4 h, then concentrated and partitioned between ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were dried over MgSO4 and concentrated. The residue was purified with Prep-HPLC to give the title compound as a white solid (Yield: 10 mg).

Workup

  1. concentrationconcentrated
  2. custompartitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. dry with materialThe organic layers were dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified with Prep-HPLC

Sources & evidence

ORD record
ord-62e157f664b34b0bb2fe2b6f7cf68c5e
Source dataset
uspto-grants-2010_08
Patent number
US07776875B2

Reaction notes

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