Methanol → 3-[[7-[(4-fluorophenyl)methyl]-9-hydroxy-5-methoxy-8-oxo-6H-pyrrolo[3,4-g]quinolin-6-yl]sulfanyl]propanoic acid

HRID 853631Notes

Reaction equation

HRID 853631 reaction equation
C[O:2][C:3](=[O:32])[CH2:4][CH2:5][S:6][CH:7]1[C:11]2[C:12]([O:21][CH3:22])=[C:13]3[C:18](=[C:19]([OH:20])[C:10]=2[C:9](=[O:23])[N:8]1[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)[N:17]=[CH:16][CH:15]=[CH:14]3.O.CO.[Li+].[OH-]>C1COCC1>[F:31][C:28]1[CH:27]=[CH:26][C:25]([CH2:24][N:8]2[C:9](=[O:23])[C:10]3[C:19]([OH:20])=[C:18]4[C:13]([CH:14]=[CH:15][CH:16]=[N:17]4)=[C:12]([O:21][CH3:22])[C:11]=3[CH:7]2[S:6][CH2:5][CH2:4][C:3]([OH:32])=[O:2])=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962Water2×HCID 3939Lithium HydroxideHCID 10479199methyl 3-[[7-[(4-fluorophenyl)methyl]-9-hydroxy-5-methoxy-8-oxo-6H-pyrrolo[3,4-g]quinolin-6-yl]sulfanyl]propanoate

Product 1

HCID 100034673-[[7-[(4-fluorophenyl)methyl]-9-hydroxy-5-methoxy-8-oxo-6H-pyrrolo[3,4-g]quinolin-6-yl]sulfanyl]propanoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 23 (150 mg, 0.329 mmol) in 3.29 mL of a 1:2:3 solution of H2O:MeOH:THF was stirred with LiOH. H2O (69 mg, 1.65 mmol) for 1 hour when LCMS demonstrated complete conversion of starting materials to product. The reaction mixture was dried under reduced pressure and the residue was suspended in water and the pH was adjusted to 11 with aqueous 1N NaOH solution. The aqueous layer was washed with EtOAc twice. The pH of the aqueous layer was then adjusted to 5 using 1N HCl and the product was extracted with CH2Cl2 under continuous extraction conditions. The organic layer was dried in vacuo to yield the product 24 as an orange solid. 1H NMR (300 MHz, CDCl3) δ 2.1 (s, 1H), 2.25-2.45 (m, 4H), 4.04 (s, 3H), 4.43 (d, 1H, J=15 Hz), 5.32 (dd, 1H, J=3, 14 Hz), 5.49 (s, 1H), 7.03 (t, 2H, J=9 Hz), 7.35 (dd, 2H, J=5, 8 Hz), 7.57 (dd, 1H, J=4, 8 Hz), 8.52 (dd, 1H, J=2, 8 Hz), 8.98 (dd, 1H, J=2, 5 H); 13C NMR (75 MHz, CD3OD) δ 21.4, 33.6, 41.9, 61.8, 61.9, 112.3, 115.7, 116.0, 123.1, 125.0, 126.5, 130.4, 130.5, 131.8, 131.8, 139.3, 142.6, 148.3, 149.6, 162.4 (d, J=245 Hz), 167.2, 175.3; 19F NMR (282.6 MHz, CDCl3) δ 62.6; EI MS (m/z) 441.4 [M−H]−, 883.1 [2M−2H]−.

Workup

  1. customThe reaction mixture was dried under reduced pressure
  2. washThe aqueous layer was washed with EtOAc twice
  3. extractionthe product was extracted with CH2Cl2 under continuous extraction conditions
  4. customThe organic layer was dried in vacuo

Sources & evidence

ORD record
ord-5f13f85d327e40cb942f6d575222da05
Source dataset
uspto-grants-2007_08
Patent number
US07253180B2

Reaction notes

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