Hydroxylamine → HCID 136054467, compound

HRID 606402Notes

Reaction equation

HRID 606402 reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([NH:14][CH2:15][C:16]2[CH:17]=[C:18]([O:22][CH2:23][CH2:24][CH2:25][C:26](O)=[O:27])[CH:19]=[CH:20][CH:21]=2)=[O:13])[NH:3]1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[NH2:40][OH:41]>C1COCC1.C(O)(C)(C)C>[OH:41][NH:40][C:26](=[O:27])[CH2:25][CH2:24][CH2:23][O:22][C:18]1[CH:17]=[C:16]([CH2:15][NH:14][C:12]([C:4]2[NH:3][C:2](=[O:1])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)=[O:13])[CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 787HydroxylamineHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 135982353HCID 135982353, compound

Product 1

HCID 136054467HCID 136054467, compoundYield 9%

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-{[3-({[(4-oxo-3,4-dihydroquinazolin-2-yl)carbonyl]amino}methyl)phenyl]oxy}butanoic acid obtained in Reference Example 44 (90.0 mg, 0.236 mmol) in THF (2 mL) were added DMF (0.02 mL) and oxalyl chloride (59.9 mg, 0.472 mmol) at 0° C., and the mixture was stirred at room temperature for 2 hr. To the reaction mixture was added a mixed solution of 50% aqueous hydroxylamine solution (0.5 mL), tert-butanol (0.5 mL) and THF (0.5 mL) at 0° C., and the mixture was stirred for 15 min. The mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC (GILSON 215LIQUD HANDLER, 322PUMP, UV/VIS-156, SHISEIDO CAPCELL PACK C-18 UG120 S-5 (20 mmφ×50 mm), mobile phase: distilled water (containing 0.1% trifluoroacetic acid)/acetonitrile (containing 0.1% trifluoroacetic acid), gradient: distilled water/acetonitrile=90/100/100, time: 10 min, flow rate: 25 mL/min, detection wavelength: 220 nm) to give a yellow powder. The obtained powder was recrystallized from ethyl acetate-hexane to give the title compound as a pale-yellow powder (8.0 mg, 9%).

Workup

  1. stirringthe mixture was stirred for 15 min
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customthe residue was purified by preparative HPLC (GILSON 215LIQUD HANDLER, 322PUMP, UV/VIS-156, SHISEIDO CAPCELL PACK C-18 UG120 S-5 (20 mmφ×50 mm), mobile phase
  4. distillationdistilled water (containing 0.1% trifluoroacetic acid)/acetonitrile (containing 0.1% trifluoroacetic acid)
  5. distillationgradient: distilled water/acetonitrile=90/100/100, time
  6. custom10 min, flow rate: 25 mL/min, detection wavelength: 220 nm) to give a yellow powder
  7. customThe obtained powder was recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-922ab1430cba49d8b75c29d8c106f3b1
Source dataset
uspto-grants-2011_03
Patent number
US07915267B2

Reaction notes

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