1,4-anhydro-2-O-(2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5,8-dichloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-deoxy-L-threo-pentitol → 1,4-anhydro-3-deoxy-2-O-{5,8-dichloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl}-L-threo-pentitol

HRID 577496Notes

Reaction equation

HRID 577496 reaction equation
C([O:8][C:9]1[C:14]([CH2:15][N:16]2[CH2:25][CH2:24][C:23]3[C:18](=[C:19]([Cl:35])[C:20]([O:27][C@@H:28]4[CH2:32][C@H:31]([CH2:33][OH:34])[O:30][CH2:29]4)=[CH:21][C:22]=3[Cl:26])[C:17]2=[O:36])=[C:13]([CH3:37])[CH:12]=[C:11]([CH3:38])[N:10]=1)C1C=CC=CC=1>FC(F)(F)C(O)=O>[Cl:26][C:22]1[CH:21]=[C:20]([O:27][C@@H:28]2[CH2:32][C@H:31]([CH2:33][OH:34])[O:30][CH2:29]2)[C:19]([Cl:35])=[C:18]2[C:23]=1[CH2:24][CH2:25][N:16]([CH2:15][C:14]1[C:9](=[O:8])[NH:10][C:11]([CH3:38])=[CH:12][C:13]=1[CH3:37])[C:17]2=[O:36]

Participants

3

Reactant 1

HCID 867237211,4-anhydro-2-O-(2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5,8-dichloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-deoxy-L-threo-pentitol

Product 1

HCID 867237221,4-anhydro-3-deoxy-2-O-{5,8-dichloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl}-L-threo-pentitolYield 40%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 1,4-anhydro-2-O-(2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5,8-dichloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-deoxy-L-threo-pentitol (296o, 36 mg, 0.065 mmol) in trifluoroacetic acid (2 mL) was stirred at room temperature for three hours. The volatiles were removed under vacuum, and the residue partitioned between ethyl acetate (20 mL) and saturated aqueous sodium bicarbonate (20 mL). The aqueous layer was back-extracted with ethyl acetate (2×20 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (eluting with a gradient of 0-10% methanol in ethyl acetate) to yield 1,4-anhydro-3-deoxy-2-O-{5,8-dichloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl}-L-threo-pentitol (Example 296, 12 mg, 40% yield), as a solid, after lyophilization. 1H NMR (400 MHz, methanol-d4) δ 7.14 (s, 1H), 6.00 (s, 1H), 4.93-5.02 (m, 1H), 4.64 (s, 2H), 3.95-4.06 (m, 2H), 3.85 (dd, J=10.39, 4.28 Hz, 1H), 3.56-3.64 (m, 1H), 3.49-3.55 (m, 1H), 3.38 (t, J=6.17 Hz, 2H), 2.80 (t, J=6.24 Hz, 2H), 2.36 (ddd, J=14.09, 7.79, 6.60 Hz, 1H), 2.18 (s, 3H), 2.14 (s, 3H), 1.84 (dd, J=13.94, 5.50 Hz, 1H).

Workup

  1. customThe volatiles were removed under vacuum
  2. customthe residue partitioned between ethyl acetate (20 mL) and saturated aqueous sodium bicarbonate (20 mL)
  3. extractionThe aqueous layer was back-extracted with ethyl acetate (2×20 mL)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography (
  7. washeluting with a gradient of 0-10% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-e31c9a3bb246460c879f9b96bc1a3e7f
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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