Methanol → HCID 86671027, compound

HRID 1037253Notes

Reaction equation

HRID 1037253 reaction equation
[ClH:1].[NH2:2][C:3]1([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[C:14](=[O:31])[C:15]4[C:16]([O:23][C:24]=3[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[C:17]([O:21]C)[N:18]=[CH:19][CH:20]=4)=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4]1.CO.O.[OH-].[Na+]>Br.CC(O)=O>[ClH:1].[NH2:2][C:3]1([C:7]2[CH:8]=[CH:9][C:10]([C:13]3[C:14](=[O:31])[C:15]4[CH:20]=[CH:19][NH:18][C:17](=[O:21])[C:16]=4[O:23][C:24]=3[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)=[CH:11][CH:12]=2)[CH2:6][CH2:5][CH2:4]1

Participants

7

Reactant 4

HCID 887MethanolHCID 962WaterHCID 14798Sodium HydroxideHCID 67067738HCID 67067738, compound

Product 1

HCID 86671027HCID 86671027, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 260Hydrogen BromideSolvent

Procedure

A solution of 3-[4-(1-amino-cyclobutyl)-phenyl]-8-methoxy-2-phenyl-pyrano[2,3-c]pyridin-4-one hydrochloride (22 mg, 0.051 mmol) in 33% hydrogen bromide solution in AcOH (0.5 mL) was heated in a microwave oven at 100° C. for 30 min. The reaction mixture was added to a mixture of MeOH (3 mL) and water (3 mL), the pH adjusted to ˜4 by addition of aqueous sodium hydroxide, and chromatographed on a 5 g C18 cartridge {gradient 35 to 70% MeOH in water+1 M HCl (0.12 mL in each 10 mL of eluent)}. Fractions containing product were concentrated in vacuo. The resultant residue was chromatographed on a 5 g C18 cartridge {gradient 35 to 70% MeOH in water+1 M HCl (0.06 mL in each 5 mL of eluent)} to give the title compound (15.1 mg, 71%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.33 (br s, 1H), 8.51 (br s, 3H), 7.48-7.33 (m, 8H), 7.28-7.26 (m, 2H), 6.61 (d, J=6.7 Hz, 1H), 2.60-2.49 (m, 4H), 2.23-2.12 (m, 1H), 1.85-1.74 (m, 1H). LCMS (Method F): RT=6.59 min, [M−H]−=383.

Workup

  1. customchromatographed on a 5 g C18 cartridge {gradient 35 to 70% MeOH in water+1 M HCl (0.12 mL in each 10 mL of eluent)}
  2. additionFractions containing product
  3. concentrationwere concentrated in vacuo
  4. customThe resultant residue was chromatographed on a 5 g C18 cartridge {gradient 35 to 70% MeOH in water+1 M HCl (0.06 mL in each 5 mL of eluent)}

Sources & evidence

ORD record
ord-f30fb1f1219a4eb4a9f7b9c00208cad8
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

Loading…