O-methylhydroxylammonium chloride → tert-Butyl (1-(4-(2-(methoxyimino)-1-methyl-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamate

HRID 1509233Notes

Reaction equation

HRID 1509233 reaction equation
[CH3:1][N:2]1[C:7](=S)[CH2:6][O:5][C:4]2[N:9]=[C:10]([C:19]3[CH:24]=[CH:23][C:22]([C:25]4([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:28][CH2:27][CH2:26]4)=[CH:21][CH:20]=3)[C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:12][C:3]1=2.[CH3:37][O:38][NH3+:39].[Cl-]>N1C=CC=CC=1>[CH3:37][O:38][N:39]=[C:7]1[CH2:6][O:5][C:4]2[N:9]=[C:10]([C:19]3[CH:24]=[CH:23][C:22]([C:25]4([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:28][CH2:27][CH2:26]4)=[CH:21][CH:20]=3)[C:11]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[CH:12][C:3]=2[N:2]1[CH3:1]

Participants

4

Reactant 2

HCID 11639O-methylhydroxylammonium chlorideHCID 87326808HCID 87326808, compound

Product 1

HCID 87326982tert-Butyl (1-(4-(2-(methoxyimino)-1-methyl-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamateYield 20.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

In a round-bottomed flask was added tert-butyl 1-(4-(1-methyl-7-phenyl-2-thioxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutylcarbamate (0.1 g, 0.199 mmol) and o-methylhydroxylamine hydrochloride (0.067 g, 0.797 mmol) in Pyridine (Volume: 2 ml). The resulting solution was stirring and heating at 70 degree for 18 h. The reaction mixture was concentrated to dryness and partitioned between ethyl acetate (20 ml) and water (20 ml). The organic phase was separated and washed with water (2×15 ml), brine (15 ml) concentrated to give the crude product which was purified by column (biotage, 25 g) eluted with ethyl acetate/cyclohexane (0-50%) to give product (21 mg) 1H NMR (500 MHz, CDCl3) 7.20-7.29 (m, 9H), 7.10 (s, 1H), 5.19 (s, 2H), 4.95 (s, 1H), 3.81 (s, 3H), 3.31 (s, 3H), 2.2-2.6 (m, 4H), 1.95-2.15 (m, 1H), 1.75-1.85 (m, 1H), 1.2-1.4 (br, 9H).

Workup

  1. temperatureheating at 70 degree for 18 h
  2. concentrationThe reaction mixture was concentrated to dryness
  3. custompartitioned between ethyl acetate (20 ml) and water (20 ml)
  4. customThe organic phase was separated
  5. washwashed with water (2×15 ml), brine (15 ml)
  6. concentrationconcentrated
  7. customto give the crude product which
  8. customwas purified by column (biotage, 25 g)
  9. washeluted with ethyl acetate/cyclohexane (0-50%)

Sources & evidence

ORD record
ord-1e0e1fa0684a41278da716b5cb078333
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

Loading…