Dimethylformamide → HCID 86683573, compound

HRID 1509146Notes

Reaction equation

HRID 1509146 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:20][C:21]4[NH:26][CH2:25][CH2:24][O:23][C:22]=4[N:27]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])(C)C.C(=O)([O-])[O-].[K+].[K+].Br[CH2:42][C:43]#N.[C:45]([O-])(O)=O.[Na+].C[N:51]([CH:53]=O)C>>[C:53]([CH2:45][N:26]1[CH2:25][CH2:24][O:23][C:22]2[N:27]=[C:18]([C:15]3[CH:14]=[CH:13][C:12]([C:8]4([NH:7][C:6](=[O:34])[O:5][CH2:1][CH2:4][CH2:42][CH3:43])[CH2:11][CH2:10][CH2:9]4)=[CH:17][CH:16]=3)[C:19]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:20][C:21]1=2)#[N:51]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 11534BromoacetonitrileHCID 516892Sodium BicarbonateHCID 123843496HCID 123843496, compound

Product 1

HCID 86683573HCID 86683573, compoundYield 19%

Procedure

To a solution of tert-butyl(1-(4-(7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamate (24 mg, 0.05 mmol) in dry DMF (1 ml) was added potassium carbonate (93 mg, 1.57 mmol) and bromoacetonitrile (110 μl, 1.57 mmol) under nitrogen. The resulting mixture was stirred for 4 hours at 80 C. 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 Biotage silica gel chromatography (gradient 0 to 60% EtOAc in cyclohexane) to give the title compound (5 mg, 19%). 1H NMR (500 MHz, CDCl3): 7.22-7.11 (9H, m), 6.93 (1H, s), 4.92 (1H, s), 4.51-4.49 (2H, m), 4.15 (2H, s), 3.39-3.37 (2H, m), 2.55-2.25 (4H, m), 1.99-1.94 (1H, m), 1.75-1.63 (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 Biotage silica gel chromatography (gradient 0 to 60% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-b8e8b36bf0504b23b3bb72720aafa5b8
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

Loading…