Methanol → HCID 86671022, compound

HRID 1037243Notes

Reaction equation

HRID 1037243 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)=[N:17][C:18]([O:21]C)=[CH:19][CH:20]=4)=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4]1.CO.O>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][C:18](=[O:21])[NH:17][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

6

Reactant 3

HCID 887MethanolHCID 962WaterHCID 67067807HCID 67067807, compound

Product 1

HCID 86671022HCID 86671022, compoundYield 91.4%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 260Hydrogen BromideSolvent

Procedure

A solution of 3-[4-(1-amino-cyclobutyl)-phenyl]-7-methoxy-2-phenyl-pyrano[2,3-b]pyridin-4-one hydrochloride (20 mg, 0.046 mmol) in 33% hydrogen bromide solution in AcOH (0.5 mL) was heated in a microwave oven at 100° C. for 30 minutes. The reaction mixture was added to a mixture of MeOH (10 mL) and water (5 mL) and the resultant solution passed through a 2 g SCX cartridge. The product was not retained by the cartridge. The washings containing the product were concentrated, the pH of the mixture was adjusted to ˜4 by addition of aqueous sodium hydroxide solution, and chromatographed on a 5 g C18 cartridge {gradient 20 to 70% MeOH in water+1M HCl (0.12 mL in each 10 mL of eluent)}. Fractions containing product were combined and concentrated in vacuo. The resulting residue was chromatographed on a 2 g C18 cartridge {gradient 20 to 60% MeOH in water+1M HCl (0.06 mL in each 5 mL of eluent)} to give the title compound (17.7 mg, 91%) as a white solid. 1H NMR (400 MHz, CD3OD): δ 8.30 (d, J=9.2 Hz, 1H), 7.50-7.47 (m, 2H), 7.45-7.38 (m, 3H), 7.34-7.29 (m, 4H), 6.73 (d, J=9.0 Hz, 1H), 2.80-2.73 (m, 2H), 2.66-2.59 (m, 2H), 2.31-2.20 (m, 1H), 2.01-1.90 (m, 1H). LCMS (Method F): RT=6.97 min, [M−H]+=383.

Workup

  1. additionThe washings containing the product
  2. concentrationwere concentrated
  3. additionthe pH of the mixture was adjusted to ˜4 by addition of aqueous sodium hydroxide solution
  4. customchromatographed on a 5 g C18 cartridge {gradient 20 to 70% MeOH in water+1M HCl (0.12 mL in each 10 mL of eluent)}
  5. additionFractions containing product
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was chromatographed on a 2 g C18 cartridge {gradient 20 to 60% MeOH in water+1M HCl (0.06 mL in each 5 mL of eluent)}

Sources & evidence

ORD record
ord-771f69bad75146a2a6fb37767cfe7bd3
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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