Formic Acid → HCID 136054516, compound

HRID 606430Notes

Reaction equation

HRID 606430 reaction equation
[CH:1](O)=[O:2].C(OC(=O)C)(=O)C.[OH:11][NH:12][CH:13]([CH:45]([CH3:47])[CH3:46])[CH2:14][S:15]([C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30][NH:31][C:32]([C:34]3[NH:43][C:42](=[O:44])[C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[N:35]=3)=[O:33])[CH:25]=2)=[CH:20][CH:19]=1)(=[O:17])=[O:16]>C1COCC1>[CH:1]([N:12]([OH:11])[CH:13]([CH:45]([CH3:47])[CH3:46])[CH2:14][S:15]([C:18]1[CH:19]=[CH:20][C:21]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30][NH:31][C:32]([C:34]3[NH:43][C:42](=[O:44])[C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[N:35]=3)=[O:33])[CH:25]=2)=[CH:22][CH:23]=1)(=[O:16])=[O:17])=[O:2]

Participants

5

Reactant 3

HCID 284Formic Acid2×HCID 7918Acetic AnhydrideHCID 136054509HCID 136054509, compound

Product 1

HCID 136054516HCID 136054516, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To formic acid (0.217 mL) was added acetic anhydride (0.054 mL, 0.576 mmol) at room temperature, and the mixture was stirred at room temperature for 2 hr. This solution was added to a suspension of N-[(4′-{[2-(hydroxyamino)-3-methylbutyl]sulfonyl}biphenyl-3-yl)methyl]-4-oxo-3,4-dihydroquinazoline-2-carboxamide obtained in Reference Example 107 (0.285 g, 0.430 mmol) and formic acid (2 mL) in THF (20 mL), and the mixture was stirred at room temperature for 4 hr. The reaction 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-s (20 mmφ×50 mm), mobile phase: distilled water (containing 0.1% trifluoroacetic acid)/acetonitrile (containing 0.1% trifluoroacetic acid), gradient: distilled water/acetonitrile=90/10→0/100, time: 10 min, flow rate: 25 mL/min, detection wavelength: 220 nm), and crystallized from EtOH-ethyl acetate-diethyl ether to give the title compound as a pale-yellow powder (0.077 g, 37%).

Workup

  1. stirringthe mixture was stirred at room temperature for 4 hr
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. distillationthe residue was purified by preparative HPLC (GILSON 215LIQUD HANDLER, 322PUMP, UV/VIS-156, SHISEIDO CAPCELL PACK C-18 UG120 S-s (20 mmφ×50 mm), mobile phase: distilled water (containing 0.1% trifluoroacetic acid)/acetonitrile (containing 0.1% trifluoroacetic acid), gradient: distilled water/acetonitrile=90/10→0/100, time: 10 min, flow rate: 25 mL/min, detection wavelength: 220 nm)
  4. customcrystallized from EtOH-ethyl acetate-diethyl ether

Sources & evidence

ORD record
ord-abcc97460e1c424489eed0d0fb89d88b
Source dataset
uspto-grants-2011_03
Patent number
US07915267B2

Reaction notes

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