Hydrochloric Acid → HCID 86683572, compound

HRID 1509144Notes

Reaction equation

HRID 1509144 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:20][C:21]4[NH:26][C:25](=[O:27])[CH2:24][O:23][C:22]=4[N:28]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[CH2:39][C:40]1[NH:41][CH:42]=[CH:43][N:44]=1.Cl.C([O-])(O)=O.[Na+]>CN(C=O)C>[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:19]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)=[CH:20][C:21]4[N:26]([CH2:39][C:40]5[NH:41][CH:42]=[CH:43][N:44]=5)[C:25](=[O:27])[CH2:24][O:23][C:22]=4[N:28]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 4257632-(chloromethyl)-1H-imidazoleHCID 516892Sodium BicarbonateHCID 67256382HCID 67256382, compound

Product 1

HCID 86683572HCID 86683572, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl(1-(4-(2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamate (26 mg, 0.05 mmol) in dry DMF (1 ml) was added sodium hydride (5 mg, 0.13 mmol) at 0° C. under nitrogen. After 1 hour at 0° C., 2-(chloromethyl)-1H-imidazole.HCl (10 mg, 0.07 mmol) was added and the resulting mixture was stirred for an additional 1 h at room temperature. A saturated solution of NaHCO3 was added and the mixture was extracted with dichloromethane (3×10 ml) using a phase separator (Isolute® SPE). The combined organic phases were concentrated to dryness under reduced pressure. The resulting residue was purified by preparative HPLC (method G, gradient 5 to 95% 0.1% FA/ACN in 0.1% FA/H2O) to give the title compound (5 mg, 17%). 1H NMR (500 MHz, CDCl3): 7.83 (1H, s), 7.22-7.15 (7H,m), 7.14-7.13 (2H,m), 6.94 (2H,s), 6.22 (1H, br s), 5.14 (2H, s), 4.98 (1H, br s), 4.83 (2H, s), 2.52-2.20 (4H, m), 2.00-1.95 (1H, m), 1.75-1.70 (1H, m), 1.44-1.15 (9H, br).

Workup

  1. extractionthe mixture was extracted with dichloromethane (3×10 ml)
  2. concentrationThe combined organic phases were concentrated to dryness under reduced pressure
  3. customThe resulting residue was purified by preparative HPLC (method G, gradient 5 to 95% 0.1% FA/ACN in 0.1% FA/H2O)

Sources & evidence

ORD record
ord-59cea12c23c44c99b82191a280b5b29a
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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