2,6-Lutidine → {3-[3-(2-{Benzyl-[(R)-2-(8-benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)ethyl]amino}ethyl)phenylcarbamoyl]-propyl}methylcarbamic Acid tert-Butyl Ester

HRID 1039813Notes

Reaction equation

HRID 1039813 reaction equation
[C:1]([O:5][C:6](CNCCCC(O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:16][C:17]1[CH:18]=[C:19]([CH2:23][CH2:24][N:25]([CH2:55][C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)[CH2:26][C@@H:27]([C:36]2[CH:45]=[CH:44][C:43]([O:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[C:42]3[C:37]=2[CH:38]=[CH:39][C:40](=[O:54])[NH:41]3)[O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[CH:20]=[CH:21][CH:22]=1.[N:62]1[C:67](C)=[CH:66][CH:65]=[CH:64][C:63]=1C.CCN=C=NCCCN(C)C.Cl.[OH:82]N1C2N=CC=CC=2N=N1>CN(C=O)C.[Cl-].[Li+].C(Cl)Cl.O>[C:1]([O:5][C:6](=[O:7])[N:62]([CH2:63][CH2:64][CH2:65][C:66](=[O:82])[NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][CH2:24][N:25]([CH2:55][C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)[CH2:26][C@@H:27]([C:36]2[CH:45]=[CH:44][C:43]([O:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[C:42]3[C:37]=2[CH:38]=[CH:39][C:40](=[O:54])[NH:41]3)[O:28][Si:29]([C:32]([CH3:33])([CH3:35])[CH3:34])([CH3:30])[CH3:31])[CH:18]=1)[CH3:67])([CH3:4])([CH3:3])[CH3:2]

Participants

10

Reactant 5

HCID 79372,6-LutidineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 216437024-[(2-tert-Butoxy-2-oxoethyl)amino]butanoic acidHCID 667816275-[(R)-2-{[2-(3-Aminophenyl)ethyl]benzylamino}-1-(tert-butyl-dimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-one

Product 1

HCID 66781581{3-[3-(2-{Benzyl-[(R)-2-(8-benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)ethyl]amino}ethyl)phenylcarbamoyl]-propyl}methylcarbamic Acid tert-Butyl Ester

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 433294Lithium ChlorideSolvent

Procedure

To a stirred solution of 4-(tert-butoxycarbonylmethylamino)butyric acid (72.0 mg, 0.331 mmol); 5-[(R)-2-{[2-(3-aminophenyl)ethyl]benzylamino}-1-(tert-butyl-dimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-one (210 mg, 0.331 mmol); 2,6-lutidine (46.5 μL, 0.398 mmol); and N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (69.8 mg, 0.364 mmol) in DMF (3 mL) at room temperature was added a solution of 1-hydroxy-7-azabenzotriazole in DMF (0.5 M, 0.729 mL, 0.364 mmol). The resulting mixture was stirred at room temperature overnight. LC-MS (Method 2-90) showed product was present (Rt 4.56 min; m/z 833.6 [M+H]+). Water was added and this mixture was diluted with aqueous 10% lithium chloride solution and DCM. The layers were separated and the organic layer was washed with aqueous 10% lithium chloride solution (2×), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was further concentrated under high vacuum to give the title compound (containing a minor amount of DMF), which was used in the next reaction without further purification.

Workup

  1. customThe layers were separated
  2. washthe organic layer was washed with aqueous 10% lithium chloride solution (2×)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. concentrationThe residue was further concentrated under high vacuum

Sources & evidence

ORD record
ord-5377de2fd0bc4ec6bff685f4d464936a
Source dataset
uspto-grants-2013_10
Patent number
US08551978B2

Reaction notes

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