Tetrahydrofuran → Benzyl [2-{[(4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}pyridin-3-yl)amino]carbonyl}-7-(1-hydroxy-1-methylethyl)quinolin-3-yl]carbamate

HRID 924392Notes

Reaction equation

HRID 924392 reaction equation
[C:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[C:9]([NH:37][C:38]([O:40][CH2:41][C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[O:39])[C:10]([C:14]([NH:16][C:17]3[CH:18]=[N:19][CH:20]=[CH:21][C:22]=3[N:23]3[CH2:28][CH2:27][CH2:26][C@H:25]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:24]3)=[O:15])=[N:11]2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH2:48]1COCC1>C[Mg]Br.CCOC(C)=O.Cl>[C:32]([O:31][C:30]([NH:29][C@H:25]1[CH2:26][CH2:27][CH2:28][N:23]([C:22]2[CH:21]=[CH:20][N:19]=[CH:18][C:17]=2[NH:16][C:14]([C:10]2[C:9]([NH:37][C:38](=[O:39])[O:40][CH2:41][C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)=[CH:8][C:7]3[C:12](=[CH:13][C:4]([C:1]([OH:3])([CH3:48])[CH3:2])=[CH:5][CH:6]=3)[N:11]=2)=[O:15])[CH2:24]1)=[O:36])([CH3:35])([CH3:34])[CH3:33]

Participants

6

Reactant 2

HCID 8028Tetrahydrofuran2×HCID 86726872tert-Butyl [(3S)-1-(3-{[(7-acetyl-3-{[(benzyloxy)carbonyl]amino}quinolin-2-yl)carbonyl]amino}pyridin-4-yl)piperidin-3-yl]carbamate

Product 1

HCID 90287190Benzyl [2-{[(4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}pyridin-3-yl)amino]carbonyl}-7-(1-hydroxy-1-methylethyl)quinolin-3-yl]carbamateYield 92%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 8857Ethyl AcetateSolventHCID 178418573HCID 178418573, compoundSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of tert-butyl [(3S)-1-(3-{[(7-acetyl-3-{[(benzyloxy)carbonyl]amino}quinolin-2-yl)carbonyl]amino}pyridin-4-yl)piperidin-3-yl]carbamate (0.100 g, 0.156 mmol) in THF (4.0 mL), methylmagnesium bromide in THF (3.0 M, 0.43 mL, 1.3 mmol) was added slowly at 0° C. under nitrogen. The reaction mixture was stirred at 0° C. for 1 h and was then allowed to warm to room temperature. The reaction mixture was diluted with EtOAc (10 mL), and 1 M HCl was slowly added to adjust the pH to 7. The aqueous layer was extracted twice with EtOAc. The organic extracts were combined, dried over Na2SO4, filtered and concentrated under reduced pressure to give the sub-title compound (94 mg, 92%). LCMS calc. for C36H43N6O6 (M+H)+: m/z=655.2. Found: 655.1.

Workup

  1. additionwas added slowly at 0° C. under nitrogen
  2. temperatureto warm to room temperature
  3. additionwas slowly added
  4. extractionThe aqueous layer was extracted twice with EtOAc
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-10920f94531d42d695822b70e8391cc9
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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