Methanol → 3-[7-(benzyloxy)-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl]-1-(cyclobutylamino)-4-hydroxyquinolin-2(1H)-one

HRID 601281Notes

Reaction equation

HRID 601281 reaction equation
[CH2:1]([O:8][C:9]1[CH:37]=[CH:36][C:12]2[NH:13][C:14]([C:19]3[C:20](=[O:35])[N:21]([N:30]=[C:31]4[CH2:34][CH2:33][CH2:32]4)[C:22]4[C:27]([C:28]=3[OH:29])=[CH:26][CH:25]=[CH:24][CH:23]=4)=[N:15][S:16](=[O:18])(=[O:17])[C:11]=2[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.[BH4-].[Li+]>O1CCCC1.Cl>[CH2:1]([O:8][C:9]1[CH:37]=[CH:36][C:12]2[NH:13][C:14]([C:19]3[C:20](=[O:35])[N:21]([NH:30][CH:31]4[CH2:32][CH2:33][CH2:34]4)[C:22]4[C:27]([C:28]=3[OH:29])=[CH:26][CH:25]=[CH:24][CH:23]=4)=[N:15][S:16](=[O:18])(=[O:17])[C:11]=2[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 4148881Lithium borohydrideHCID 1363739433-[7-(benzyloxy)-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl]-1-(cyclobutylideneamino)-4-hydroxyquinolin-2(1H)-one

Product 1

HCID 1363740373-[7-(benzyloxy)-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl]-1-(cyclobutylamino)-4-hydroxyquinolin-2(1H)-oneYield 33%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
25 °C

Procedure

The product of Example 304G (0.178 g, 0.35 mmol) in tetrahydrofuran (3 mL) at 0° C. was treated with methanol (0.025 mL, 0.70 mmol), followed by dropwise addition of a 2.0 M solution of lithium borohydride in tetrahydrofuran (0.260 mL, 0.52 mmol), stirred at 25° C. for one hour, and diluted with 1 N HCl. The resulting precipitate was filtered and dried. The solid was dissolved in tetrahydrofuran and absorbed onto silica gel by evaporating to dryness. The resulting silica was loaded onto a 2 g Alltech sep pack and eluted with dichloromethane to give the title compound (0.059 g, 33%). MS (ESI−) m/z 515 (M−H)−. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.55 (m, 1 H) 1.71 (m, 1 H) 2.04 (m, 4 H) 3.77 (m, 1 H) 5.26 (s, 2 H) 6.57 (d, J=5.15 Hz, 1 H) 7.45 (m, 8 H) 7.64 (d, J=9.56 Hz, 1 H) 7.88 (m, 1 H) 8.05 (d, J=8.46 Hz, 1 H) 8.17 (m, 1 H).

Workup

  1. filtrationThe resulting precipitate was filtered
  2. customdried
  3. dissolutionThe solid was dissolved in tetrahydrofuran
  4. customabsorbed onto silica gel
  5. customby evaporating to dryness
  6. washeluted with dichloromethane

Sources & evidence

ORD record
ord-d022e156dc4049e883bf5d5887f2117d
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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