Chloroacetone → HCID 53261991, compound

HRID 1509132Notes

Reaction equation

HRID 1509132 reaction equation
C(OC(=O)[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[CH:20][C:21]4[N:26]([CH2:27][C:28](=[O:30])[CH3:29])[C:25](=[O:31])[CH2:24][O:23][C:22]=4[N:32]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)(C)(C)C.[H-].[Na+].ClCC(=O)C.[NH4+].[Cl-]>CN(C=O)C>[NH2:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:19]([C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)=[CH:20][C:21]4[N:26]([CH2:27][C:28](=[O:30])[CH3:29])[C:25](=[O:31])[CH2:24][O:23][C:22]=4[N:32]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1

Participants

6

Reactant 4

HCID 6571ChloroacetoneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 131734402HCID 131734402, compound

Product 1

HCID 53261991HCID 53261991, compoundYield 73.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl(1-(4-(2-oxo-1-(2-oxopropyl)-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamate (60 mg, 0.13 mmol) in dry DMF (2.5 mL) was added sodium hydride (5 mg, 0.14 mmol) at 0° C. under nitrogen. After 1 h at 0° C., chloroacetone (11 □L, 0.14 mmol) was added and the resulting mixture was stirred for two hours at 0° C. A saturated solution of NH4Cl was added while stirring, keeping the temperature below 10° C. The resulting mixture was extracted with dichloromethane (3×) using a phase separator (Isolute® SPE). The combined organic phases were concentrated to dryness under reduced pressure. The resulting residue was purified by Biotage chromatography (silica, hexane:ethyl acetate, gradient elution from 100:0 to 55:45) to give the desired product as a white solid (41 mg, 60% yield). 1H NMR (500 MHz, CDCl3): 7.12-7.28 (9H, m), 6.82 (1H,S), 4.95 (2H, s), 4.54 (2H, s), 2.36-2.52 (4H, m), 2.23 (3H, s), 1.98-2.12 (1H, m), 1.69-1.75 (1H, m), 1.47 (9H, br s). 1H NMR (Method A): RT=6.87 min, M+H+=528.

Workup

  1. stirringwhile stirring
  2. customthe temperature below 10° C
  3. extractionThe resulting mixture was extracted with dichloromethane (3×)
  4. concentrationThe combined organic phases were concentrated to dryness under reduced pressure
  5. customThe resulting residue was purified by Biotage chromatography (silica, hexane:ethyl acetate, gradient elution from 100:0 to 55:45)

Sources & evidence

ORD record
ord-edc8d6efcaee48058689e65b476e8cc6
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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