Pyridine → HCID 118340312, compound

HRID 1477152Notes

Reaction equation

HRID 1477152 reaction equation
Cl[C:2](=[O:25])[C@@H:3]([NH:7][C:8](=[O:24])[O:9][CH2:10][CH:11]1[C:23]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[C:17]2[C:12]1=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:4]([CH3:6])[CH3:5].[F:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:28]=1[NH:34][C:35]([CH:37]1[C:45]([CH3:47])([CH3:46])[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[NH:38]1)=[O:36].N1C=CC=CC=1>C(Cl)Cl.CCOC(C)=O>[F:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:28]=1[NH:34][C:35]([CH:37]1[C:45]([CH3:47])([CH3:46])[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[N:38]1[C:2](=[O:25])[C@@H:3]([NH:7][C:8](=[O:24])[O:9][CH2:10][CH:11]1[C:23]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[C:17]2[C:12]1=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:4]([CH3:6])[CH3:5])=[O:36]

Participants

6

Reactant 3

HCID 1049PyridineHCID 10915303(S)-(9H-Fluoren-9-yl)methyl (1-chloro-3-methyl-1-oxobutan-2-yl)carbamateHCID 117872111HCID 117872111, compound

Product 1

HCID 118340312HCID 118340312, compoundYield 114.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-(9H-fluoren-9-yl)methyl 1-chloro-3-methyl-1-oxobutan-2-ylcarbamate (0.11 g, 307 μmol, Eq: 3.1) was added to a solution of N-(2,6-difluorophenyl)-3,3-dimethylindoline-2-carboxamide (30 mg, 99.2 μmol, Eq: 1.00) and pyridine (40 μL, 496 μmol, Eq: 5) in DCM (1 mL) and the resulting solution was stirred at rt for 3 h. The reaction mixture was diluted with EtOAc (20 mL) and washed with 1 M aqueous HCl (10 mL), 1 M aqueous NaOH (10 mL) and brine (10 mL), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 4 g, 0% to 30% EtOAc in hexanes) to give (S)-(9H-fluoren-9-yl)methyl 1-(2-(2,6-difluorophenylcarbamoyl)-3,3-dimethylindolin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate as a viscous oil (71 mg).

Workup

  1. washwashed with 1 M aqueous HCl (10 mL), 1 M aqueous NaOH (10 mL) and brine (10 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe crude material was purified by flash chromatography (silica gel, 4 g, 0% to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-68f327b2aee74129a7b2568a4fa9af72
Source dataset
uspto-grants-2016_08
Patent number
US09403768B2

Reaction notes

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